Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “evolution of cell shape”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 577 records · Page 32Linked to original sources
PubMed2006

Intracellular demography and the dynamics of Salmonella enterica infections.

An understanding of within-host dynamics of pathogen interactions with eukaryotic cells can shape the development of effective preventive measures and drug regimes. Such investigations have been hampered by the difficulty of identifying and observing directly, within live tissues, the multiple key variables that underlay infection processes. Fluorescence microscopy data on intracellular distributions of Salmonella enterica serovar Typhimurium (S. Typhimurium) show that, while the number of infected cells increases with time, the distribution of bacteria between cells is stationary (though highly skewed). Here, we report a simple model framework for the intensity of intracellular infection that links the quasi-stationary distribution of bacteria to bacterial and cellular demography. This enables us to reject the hypothesis that the skewed distribution is generated by intrinsic cellular heterogeneities, and to derive specific predictions on the within-cell dynamics of Salmonella division and host-cell lysis. For within-cell pathogens in general, we show that within-cell dynamics have implications across pathogen dynamics, evolution, and control, and we develop novel generic guidelines for the design of antibacterial combination therapies and the management of antibiotic resistance.

Animals↗
PubMed2005

Visualization of diffuse centromeres with centromere-specific histone H3 in the holocentric plant Luzula nivea.

Although holocentric species are scattered throughout the plant and animal kingdoms, only holocentric chromosomes of the nematode worm Caenorhabditis elegans have been analyzed with centromeric protein markers. In an effort to determine the holocentric structure in plants, we investigated the snowy woodrush Luzula nivea. From the young roots, a cDNA encoding a putative centromere-specific histone H3 (LnCENH3) was successfully isolated based on sequence similarity among plant CENH3s. The deduced amino acid sequence was then used to raise an anti-LnCENH3 antibody. Immunostaining clearly revealed the diffuse centromere-like structure that appears in the linear shape at prophase to telophase. Furthermore, it was shown that the amount of LnCENH3 decreased significantly at interphase. The polar side positioning on each chromatid at metaphase to anaphase also confirmed that LnCENH3 represents one of the centromere-specific proteins in L. nivea. These data from L. nivea are compared with those from C. elegans, and common features of holocentric chromosomes are discussed.

Amino Acid Sequence↗
PubMed2003

Concordia discors: duality in the origin of the vertebrate tail.

The vertebrate tail is an extension of the main body axis caudal to the anus. The developmental origin of this structure has been a source of debate amongst embryologists for the past century. Some view tail development as a continuation of the morphogenetic processes that shape the head and trunk (i.e. gastrulation). The alternative view, secondary development, holds that the tail forms in a manner similar to limb development, i.e. by secondary induction. Previous developmental studies have provided support for both views. Here I revisit these studies, describing caudal morphogenesis in select vertebrates, the associated genes and developmental defects, and, as a relevant aside, consider the developmental and evolutionary relationships of primary and secondary neurulation. I conclude that caudal development enlists both gastrulation and secondary induction, and that the application of recent high-resolution cell labelling technology may clarify how these discordant programmes interact in building the vertebrate tail.

Animals↗
PubMed2002

A new look at an old visual system: structure and development of the compound eyes and optic ganglia of the brine shrimp Artemia salina Linnaeus, 1758 (Branchiopoda, anostraca).

Compared to research carried out on decapod crustaceans, the development of the visual system in representatives of the entomostracan crustaceans is poorly understood. However, the structural evolution of the arthropod visual system is an important topic in the new debate on arthropod relationships, and entomostracan crustaceans play a key role in this discussion. Hence, data on structure and ontogeny of the entomostracan visual system are likely to contribute new aspects to our understanding of arthropod phylogeny. Therefore, we explored the proliferation of neuronal stem cells (in vivo incorporation of bromodeoxyuridine) and the developmental expression of synaptic proteins (immunohistochemistry against synapsins) in the developing optic neuropils of the brine shrimp Artemia salina Linnaeus, 1758 (Crustacea, Entomostraca, Branchiopoda, Anostraca) from hatching to adulthood. The morphology of the adult visual system was examined in serial sections of plastic embedded specimens. Our results indicate that the cellular material that gives rise to the visual system (compound eyes and two optic ganglia) is contributed by the mitotic activity of neuronal stem cells that are arranged in three band-shaped proliferation zones. Synapsin-like immunoreactivity in the lamina ganglionaris and the medulla externa initiated only after the anlagen of the compound eyes had already formed, suggesting that the emergence of the two optic neuropils lags behind the proliferative action of these stem cells. Neurogenesis in A. salina is compared to similar processes in malacostracan crustaceans and possible phylogenetic implications are discussed.

Age Factors↗
PubMed2002

Crystal structures of two rat MHC class Ia (RT1-A) molecules that are associated differentially with peptide transporter alleles TAP-A and TAP-B.

Antigenic peptides are loaded onto class I MHC molecules in the endoplasmic reticulum (ER) by a complex consisting of the MHC class I heavy chain, beta(2)-microglobulin, calreticulin, tapasin, Erp57 (ER60) and the transporter associated with antigen processing (TAP). While most mammalian species transport these peptides into the ER via a single allele of TAP, rats have evolved different TAPs, TAP-A and TAP-B, that are present in different inbred strains. Each TAP delivers a different spectrum of peptides and is associated genetically with distinct subsets of MHC class Ia alleles, but the molecular basis for the conservation (or co-evolution) of the two transporter alleles is unknown. We have determined the crystal structures of a representative of each MHC subset, viz RT1-A(a) and RT1-A1(c), in association with high-affinity nonamer peptides. The structures reveal how the chemical properties of the two different rat MHC F-pockets match those of the corresponding C termini of the peptides, corroborating biochemical data on the rates of peptide-MHC complex assembly. An unusual sequence in RT1-A1(c) leads to a major deviation from the highly conserved beta(3)/alpha(1) loop (residues 40-59) conformation in mouse and human MHC class I structures. This loop change contributes to profound changes in the shape of the A-pocket in the peptide-binding groove and may explain the function of RT1-A1(c) as an inhibitory natural killer cell ligand.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2003

Siliceous spicules and skeleton frameworks in sponges: origin, diversity, ultrastructural patterns, and biological functions.

Silica deposition is a fundamental process in sponges. Most sponges in the Classes Demospongiae and Hexactinellida secrete siliceous elements, which can subsequently fuse, interlock with each other, or form three-dimensional structures connected by spongin. The resulting skeletal frameworks allow sponges to grow upwards and facilitate water exchange with minimal metabolic cost. Several studies on sponge skeletogenesis have been published. We are beginning to understand the mechanisms of spicule secretion and the role of spicules and skeletal frameworks in the biology, ecology, and evolution of sponges. Molecular techniques and ecological experiments have demonstrated the genetic control of the process and the contribution of environmental factors to the expression of a sponge spicule, respectively. However, other classic topics such as the role of membranes in silicon transport or whether spicules are formed in situ or secreted anywhere in the sponge mesohyl and then transported to the skeletal framework require further investigation. We review the process of silica deposition in sponges at the molecular and cellular levels, as well as the biological and ecological functions of spicules and skeletons. The genetic control of spicule shapes makes them useful in the reconstruction of sponge phylogeny, although recent experiments have demonstrated the influence of environmental factors in modulating spicule size, shape, and the presence or absence of one or more spicule types. The implications of such variations in sponge taxonomy may be important. Besides supporting sponge cells, spicules can help larvae stay buoyant while in the plankton or reach the bottom at settlement, enhance reproduction success, or catch prey. Conversely, the role of spicules and skeletons in deterring predation has not been demonstrated. Knowledge of several aspects is still based on a single or a few species and extrapolations should be made only with caution. With the advent of new molecular techniques, new lines of research are presently open and active in this field.

Animals↗
PubMed2026

The genomic alchemist's arsenal: A comprehensive review of gene recruitment, regulatory rewiring, and the evolutionary arms race in snake envenomation.

Snake venom represents a striking example of evolutionary innovation, in which ancestral physiological gene networks have been co-opted into potent biochemical weapons. Advances in multi-omics, single-cell genomics, and structural bioinformatics have catalyzed a conceptual shift from descriptive toxin cataloging to a systems-level understanding of venom evolution, regulation, and function. This Review integrates genomic, cellular, and structural perspectives to delineate the molecular architecture underpinning venom diversification and target-site co-evolution. Emphasis is placed on regulatory mechanisms driving rapid expression plasticity, including super-enhancer activity, transposable element insertion, spatial heterogeneity within the venom gland, and non-coding RNA-mediated modulation. At the protein level, the review examines how hypervariable toxins engage in structural arms races with prey targets, and how multi-toxin complex formation, functional synergy, and molecular dynamics simulations inform models of lethality and resistance. A comparative framework is provided by contrasting high-potency predatory snake venoms with low-potency defensive venoms of hymenopterans such as bees and wasps, revealing how ecological selective pressures shape toxin potency, composition, and target specificity across taxa. Finally, current translational strategies are evaluated, with a focus on the relative merits of recombinant human monoclonal antibodies versus catalytic-site small-molecule inhibitors as deployable interventions for snakebite. By synthesizing evolutionary genomics, structural biology, comparative toxinology, and synthetic antivenomics, this Review outlines a predictive framework for anticipating venom evolutionary trajectories and for designing broad-spectrum, next-generation therapeutics.

Animals↗
PubMed2003

Spontaneous mutation in mice provides new insight into the genetic mechanisms that pattern the seminal vesicles and prostate gland.

The seminal vesicles and prostate gland are anatomically adjacent male sex-accessory glands. Although they arise from different embryonic precursor structures and express distinct sets of secretory proteins, these organs share common features in their developmental biology. A key shared developmental feature is the elaboration of complex secretory epithelia with tremendous surface area from simple precursor structures with juxtaposed epithelial and mesenchymal cells. In this study, new insight into the nature of the biological processes that underlie glandular morphogenesis is achieved by analyzing the phenotypes present in mice that harbor a spontaneous mutation, seminal vesicle shape (svs), previously identified for causing altered seminal vesicle morphology in adults. An examination of seminal vesicle development in svs mice provides the first evidence that the concurrent processes of epithelial branching and epithelial infolding are distinct processes under separate genetic control. It also provides the first direct evidence that the thickness and topology of the smooth muscle layer in the seminal vesicles are determined by interaction with the glandular epithelium during the branching process. In addition, the seminal vesicle phenotype in svs mice is shown to phenocopy the morphologic form present in certain other mammals such as the guinea pig, raising the possibility that the svs mutation is the sort of variant that arises during evolution. By also including an investigation of the prostate gland, this study also identifies previously unrecognized phenotypes in svs prostates, including increased gland size and dramatically reduced levels of branching morphogenesis. Finally, this study advances the goal of identifying the svs gene by mapping the svs mutation relative to known molecular markers and testing Fgfr2 as a candidate gene. The finding that the svs mutation maps to a genomic region syntenic to a region frequently deleted in human prostate tumors, together with the prostatic phenotype present in svs mice, further raises the interesting possibility that the svs mutation will identify a candidate prostate tumor suppressor gene.

Animals↗
PubMed1995

Development of the olfactory and accessory lobes in the American lobster: an allometric analysis and its implications for the deutocerebral structure of decapods.

The allometric changes characterizing the growth of the deutocerebrum (midbrain) of the American lobster (Homarus americanus) are studied using computerized three-dimensional reconstructions of serial brain sections. During the embryogenesis of the midbrain, the paired accessory lobes (higher order processing areas) appear later than the paired olfactory lobes (primary olfactory centers), but the former grow faster from their emergence until metamorphosis. The accessory lobes, as they enlarge, shift progressively from a medial to a posterior position in the lateral deutocerebrum. In early juvenile stages the accessory lobes are one of the largest neuropils of the brain. However, these lobes stop growing in adult animals, whereas the brain and olfactory lobes continue to enlarge, albeit at a slow rate. The overall shape of the brain and the relative proportions and locations of the deutocerebral neuropils and associated cell clusters of various lobster ontogenetic stages are similar to those of selected adult decapods. In addition, the relation between deutocerebral organization and brain size seem parallel during lobster development and across crustacean species. Measurements of the brains of 13 species of decapods (illustrated in Sandeman et al. [1993] J. Exp. Zool. 265:112, plus Homarus) indicate the following trends: Small brains possess olfactory lobes but no accessory lobes, larger brains possess accessory lobes that are medial and small relative to the olfactory lobes, and the largest brains contain relatively voluminous posterior accessory lobes. These observations indicate that some differences in the organization of the deutocerebrum are related to absolute brain size in crustaceans and suggest that ontogenetic scaling of proportions may apply to the deutocerebral neuropils of decapods. Peramorphosis and paedomorphosis in the evolution of the decapod brain are considered.

Animals↗
PubMed2003

Structural dynamics of eukaryotic chromosome evolution.

Large-scale genome sequencing is providing a comprehensive view of the complex evolutionary forces that have shaped the structure of eukaryotic chromosomes. Comparative sequence analyses reveal patterns of apparently random rearrangement interspersed with regions of extraordinarily rapid, localized genome evolution. Numerous subtle rearrangements near centromeres, telomeres, duplications, and interspersed repeats suggest hotspots for eukaryotic chromosome evolution. This localized chromosomal instability may play a role in rapidly evolving lineage-specific gene families and in fostering large-scale changes in gene order. Computational algorithms that take into account these dynamic forces along with traditional models of chromosomal rearrangement show promise for reconstructing the natural history of eukaryotic chromosomes.

Animals↗
PubMed2003

Larval development of Myzostoma cirriferum (Myzostomida).

The larval development of Myzostoma cirriferum is described by means of SEM, TEM, and cLSM. It is similar to that of other myzostomids and includes three stages: the protrochophore, the trochophore, and the metatrochophore. The protrochophore is a ball-shaped larva present in culture from 18-48 h after egg laying. It has no internal organs and its body is made of three cell types: covering cells and ciliated cells that are external and surrounded by a cuticle, and resting cells that fill the blastocoel. The trochophore is a pear-shaped larva that develops 20-72 h after egg laying; the body includes the same three cell types as the previous stage. The metatrochophore is a pear-shaped larva that develops between 40 h and 14 days and is characterized by the presence of two bundles of four chaetae. When fully developed, the metatrochophore has a digestive system (made of a pharynx, an esophagus, and a blind digestive pouch), two pairs of protonephridia, and a nervous system composed of a supraesophageal ganglion, circumesophageal connectives, and dorsal and ventral nerves. Metamorphosis generally occurs 7 days after egg laying. At that time, the metatrochophore loses its chaetae and becomes pleated ventrally. This ultrastructural analysis suggests that chaetae and the five ventral longitudinal nerve cords of M. cirriferum metatrochophores are homologous structures to those observed in some polychaete trochophores. Coupled with recent phylogenetic analyses, where the Myzostomida are placed outside the Annelida, homologies between myzostomid and polychaete larvae support the view that a trochophore appeared early during the spiralian evolution.

Animals↗
PubMed1980

Ultrastructure of serotonin-containing cells in the pineal organ of Lampetra planeri (Petromyzontidae).

The ultrastructure of the "cells containing residual bodies" (Collin, 1969) was investigated in the pineal organ of Lampetra planeri. These cells are characterized by their indoleamine metabolism (Meiniel, 1978: Meiniel and Hartwig, 1980). Morphologically, they belong mainly to two types: (1) a photoreceptor cell type, and (2) a pinealocyte cell type. The first type is present in the pineal sensory epithelium and in the atrium, while the second is observed in the deep part of the atrium. Intermediate cell types are rare. All these cells are characterized by the presence of voluminous dense bodies, the 5-HT-storing structures, in their cytoplasm. The elongated cone-type photoreceptor cells show a segmental organization and well-developed outer segments consisting of short disks (2--3 micrometer), while their basal pedicles form synapses with the dendritic processes of neurons. The pinealocytes are spherical or oval in shape, their receptor poles being regressed to cilia of the 9 + 0 type. In these cells, no synaptic ribbons have to date been observed. In both cell types a Golgi apparatus is present producing dense granules 130 nm in diameter and a polymorphous dense material. The photoreceptor cells most probably respond to light and transmit a sensory (i.e., nervous) message. In addition, they produce and metabolize indoleamines, probably including, melatonin (*Meiniel, 1978; Meiniel and Hartwig, 1980). The pinealocytes, in spite of their loss of direct photosensitivity, retain their capacity to metabolize indoleamines (Meiniel, 1978; Meiniel and Hartwig, 1980). The presence, in the same pineal organ, of another photoreceptor cell type (cf. Collin, 1969--1971) differing morphologically as well as biochemically (no detectable indoleamine metabolism) from the photoreceptor cell type described in the present investigation, points to the existence of two different sensory cell lines: (1) a "pure " photoreceptor line, and (2) a photoneuroendocrine line. The phylogenetic evolution of these two cell lines is discussed in terms of functional analogy.

Animals↗
PubMed2003

Cold hibernated elastic memory foams for endovascular interventions.

Cold hibernated elastic memory (CHEM) polyurethane-based foam is a new shape memory polymeric self-deployable structure. Standard cytotoxicity and mutagenicity tests were conducted on CHEM in vitro, to ensure biocompatibility before studying potential medical applications. In vivo, lateral wall aneurysms were constructed on both carotid arteries of eight dogs. Aneurysms were occluded per-operatively with CHEM blocks. In two dogs, CHEM embolization was compared with gelatin sponge fragment embolization. Internal maxillary arteries (Imax) were also occluded with CHEM using a 6F transcatheter technique. Angiography and pathology were used to study the evolution of aneurysms and Imax at 3 and 12 weeks. Imax embolized with CHEM foam remained occluded at 3 weeks. Most aneurysms embolized with CHEM showed a small residual crescent of opacification at initial angiography, but angiographic scores were significantly better at 3 weeks. Thick neointima formation over the CHEM at the neck of aneurysms was demonstrated at pathology. The foamy nature of CHEM favours the ingrowth of cells involved in neointima formation. New devices for endovascular interventions could be designed using CHEM's unique physical properties.

Aneurysm↗
PubMed2026

Insect immune systems: same same but different but still same.

Insects are the most diverse group of animals in nature, occupying nearly every ecological niche and playing central roles as pollinators, pests, and disease vectors. Despite this vast diversity, insects rely on a set of conserved yet evolutionarily adaptable immune pathways to defend against pathogens. Early studies in insect immunity have laid the foundation for human immunology, and recent advances in genomic and transgenic technologies have renewed interest in understanding how immune responses vary across insect orders. Insects are highly diverse in their immune systems; each species has unique immune responses that help fight infections from specific pathogens. Nevertheless, they share multiple aspects of recognition, regulation, and effector mechanisms. This review focuses on current knowledge of the immune systems of major insect lineages to highlight both shared signaling pathways, immune cells, and humoral factors, as well as lineage-specific responses that reflect distinct ecological pressures that have shaped the host-microbe interactions. Comparing different insect species and orders not only provides insights into the evolutionary divergences and convergences of immune system features but also offers complementary knowledge among species within the same order, helping fill existing gaps. Understanding these evolutionary patterns not only deepens our understanding of insect immunity but also informs the development of transgenic strategies to disrupt pathogen transmission in key vector species.

Animals↗
PubMed2002

Effects of salinity stress on photosystem II function in cyanobacterial Spirulina platensis cells.

The changes in PSII photochemistry in Spirulina platensis cells exposed to salinity stress (0-0.8 M NaCl) for 12 h were studied. Salinity stress induced a decrease in oxygen evolution activity, which correlated with the decrease in the quantum yield of PSII electron transport (PhiPSII). Phycocyanin content decreased significantly while chlorophyll content remained unchanged in salt-stressed cells. Salinity stress induced an increase in non-photochemical quenching (qN) and a decrease in photochemical quenching (qP). Analyses of the polyphasic fluorescence transients (OJIP) showed that with the increase in salt concentration, the fluorescence yield at the phases J, I and P declined sharply and the transient almost levelled off at salt concentration of 0.8 M NaCl. The effects of DCMU on the polyphasic rise of fluorescence transients decreased significantly. Salinity stress resulted in a decrease in the efficiency of electron transfer from QA- to QB. The slope at the origin of the relative variable fluorescence curves (dV/dto) and the relative variable fluorescence at phase J (VJ) increased in the absence of DCMU, but decreased in the presence of DCMU. The shape of the relative variable fluorescence transients in salt-stressed cells was comparable to that of the control cells incubated with DCMU. The results in this study suggest that salt stress inhibited the electron transport at both donor and acceptor sides of PSII, resulted in damage to phycobilisome and shifted the distribution of excitation energy in favour of PSI.

Journal Article↗
PubMed1997

From essential to beneficial: glycoprotein D loses importance for replication of bovine herpesvirus 1 in cell culture.

Glycoprotein D (gD) of bovine herpesvirus 1 (BHV-1) has been shown to be an essential component of virions involved in virus entry. gD expression in infected cells is also required for direct cell-to-cell spread. Therefore, BHV-1 gD functions are identical in these aspects to those of herpes simplex virus 1 (HSV-1) gD. In contrast, the gD homolog of pseudorabies virus (PrV), although essential for penetration, is not necessary for direct cell-to-cell spread. Cocultivation of cells infected with phenotypically gD-complemented gD- mutant BHV-1/80-221 with noncomplementing cells resulted in the isolation of the cell-to-cell-spreading gD-negative mutant ctcs+BHV-1/80-221, which was present in the gD-null BIV-1 stocks. ctcs+BHV-1/80-221 could be propagated only by mixing infected with uninfected cells, and virions released into the culture medium were noninfectious. Marker rescue experiments revealed that a single point mutation in the first position of codon 450 of the glycoprotein H open reading frame, resulting in a glycine-to-tryptophan exchange, enabled complementation of the gD function for cell-to-cell spread. After about 40 continuous passages of ctcs+BHV-1/80-221-infected cells with noninfected cells, the plaque morphology in the cultures started to change from roundish to comet shaped. Cells from such plaques produced infectious gD- virus, named gD-infBHV-1, which entered cells much more slowly than wild-type BHV-1. In contrast, integration of the gD gene into the genomes of gD-infBHV-1 and ctcs+BHV-1/80-221 resulted in recombinants with accelerated penetration in comparison to wild-type virions. In summary, our results demonstrate that under selective conditions, the function of BHV-1 gD for direct cell-to-cell spread and entry into cells can be compensated for by mutations in other viral (glyco)proteins, leading to the hypothesis that gD is involved in formation of penetration-mediating complexes in the viral envelope of which gH is a component. Together with results for PrV, varicella-zoster virus, which lacks a gD homolog, and Marek's disease virus, whose gD homolog is not essential for infectivity, our data may open new insights into the evolution of alphaherpesviruses.

Animals↗
PubMedDate not supplied

Scrambled eggs: mechanical forces as ecological factors in early development.

Many ecological interactions involve, at some level, mechanical forces and the movements or structural deformations they produce. Although the most familiar examples involve the functional morphology of adult structures, all life history stages (not just the adults) are subject to the laws of physics. Moreover, the success of every lineage depends on the success of every life history stage (again, not just the adults). Therefore, insights gained by using mechanical engineering principles and techniques to study ecological interactions between gametes, embryos, larvae, and their environment are essential to a well-rounded understanding of development, ecology, and evolution. Here I draw on examples from the literature and my own research to illustrate ways in which mechanical forces in the environment shape development. These include mechanical forces acting as selective factors (e.g., when coral gamete size and shape interact with turbulent water flow to determine fertilization success) and as developmental cues (e.g., when plant growth responds to gravity or bone growth responds to mechanical loading). I also examine the opposite cause-and-effect relationship by considering examples in which the development of organisms impacts ecologically relevant mechanical forces. Finally, I discuss the potential for ecological pattern formation as a result of feedback loops created by such bidirectional interactions between developmental processes and mechanical forces in the environment.

Animals↗
PubMed1996

Molecular evolution of bacterial beta-lactam resistance.

BACKGROUND: Two groups of penicillin-destroying enzymes, the class A and class C beta-lactamases, may have evolved from bacterial transpeptidases that transfer X-D-Ala-D-Ala peptides to the growing peptidoglycan during cell wall synthesis. Both the transpeptidases and the beta-lactamases are acylated by beta-lactam antibiotics such as penicillin, which mimic the peptide, but breakdown and removal of the antibiotic is much faster in the beta-lactamases, which lack the ability to process D-Ala-D-Ala peptides. Stereochemical factors driving this evolution in specificity are examined. RESULTS: We have compared the crystal structures of two classes of beta-lactamases and a beta-lactam-sensitive D-alanyl-D-alanine carboxy-peptidase/transpeptidase (DD-peptidase). The class C beta-lactamase is more similar to the DD-peptidase than to another beta-lactamase of class A. CONCLUSIONS: The two classes of beta-lactamases appear to have developed from an ancestral protein along separate evolutionary paths. Structural differentiation of the beta-lactamases from the DD-peptidases appears to follow differences in substrate shapes. The structure of the class A beta-lactamase has been further optimized to exclude D-alanyl peptides and process penicillin substrates with near catalytic perfection.

Anti-Bacterial Agents↗