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Desulfovibrio desulfuricans iron hydrogenase: the structure shows unusual coordination to an active site Fe binuclear center.

BACKGROUND: Many microorganisms have the ability to either oxidize molecular hydrogen to generate reducing power or to produce hydrogen in order to remove low-potential electrons. These reactions are catalyzed by two unrelated enzymes: the Ni-Fe hydrogenases and the Fe-only hydrogenases. RESULTS: We report here the structure of the heterodimeric Fe-only hydrogenase from Desulfovibrio desulfuricans - the first for this class of enzymes. With the exception of a ferredoxin-like domain, the structure represents a novel protein fold. The so-called H cluster of the enzyme is composed of a typical [4Fe-4S] cubane bridged to a binuclear active site Fe center containing putative CO and CN ligands and one bridging 1, 3-propanedithiol molecule. The conformation of the subunits can be explained by the evolutionary changes that have transformed monomeric cytoplasmic enzymes into dimeric periplasmic enzymes. Plausible electron- and proton-transfer pathways and a putative channel for the access of hydrogen to the active site have been identified. CONCLUSIONS: The unrelated active sites of Ni-Fe and Fe-only hydrogenases have several common features: coordination of diatomic ligands to an Fe ion; a vacant coordination site on one of the metal ions representing a possible substrate-binding site; a thiolate-bridged binuclear center; and plausible proton- and electron-transfer pathways and substrate channels. The diatomic coordination to Fe ions makes them low spin and favors low redox states, which may be required for catalysis. Complex electron paramagnetic resonance signals typical of Fe-only hydrogenases arise from magnetic interactions between the [4Fe-4S] cluster and the active site binuclear center. The paucity of protein ligands to this center suggests that it was imported from the inorganic world as an already functional unit.

Amino Acid Sequence↗

Angiotensin II and the transcription factor Rel/NF-kappaB link environmental water shortage with memory improvement.

One of the essential requirements even in the most ancient life forms is to be able to preserve body fluid medium. In line with such requirement, animals need to perform different behaviors to cope with water shortages. As angiotensin II (ANGII) is involved on a widespread range of functions in vertebrates, including memory modulation, an integrative role, in response to an environmental water shortage, has been envisioned. Previous work on the semi-terrestrial and brackish-water crab Chasmagnathus granulatus showed that endogenous ANGII enhanced an associative long-term memory and, in addition, that high salinity environment induces both an increase of brain ANGII levels and memory improvement. Here, we show that in the crab Chasmagnathus air exposure transiently increases blood sodium concentration, significantly increases brain ANGII immunoreactivity, and has a facilitatory effect on memory that is abolished by a non-selective ANGII receptor antagonist, saralasin. Furthermore, Rel/NF-kappaB, a transcription factor activated by ANGII in mammals and during memory consolidation in Chasmagnathus brain, is induced in the crab's brain by air exposure. Moreover, nuclear brain NF-kappaB is activated by ANGII, and this effect is reversed by saralasin. Our results constitute the first demonstration in an invertebrate that cognitive functions are modulated by an environmental stimulus through a neuropeptide and give evolutionary support to the role of angiotensins in memory processes. Moreover, these results suggest that angiotensinergic system is preserved across evolution not only in its structure and molecular mechanisms, but also in its capability of coordinating specific adaptative responses.

Air↗

Significance of the need for sperm capacitation before fertilization in eutherian mammals.

In order to fertilize, the spermatozoa of eutherian mammals must undergo capacitation in the female tract. The subcellular changes involved in capacitation finally seem to permit the influx of Ca2+ required for onset of the acrosome reaction, and they result also in a hyperactivated form of motility. However, why capacitation has appeared as an essential prerequisite for eutherian fertilization is unknown. Both these facets of capacitation may reflect new cellular control mechanisms for regulating the sperm's activities, necessitated by evolutionary change in the oocyte. The first may reflect a loss of the oocyte's stimulation of the acrosome reaction, and the second a concomitant appearance of unusually formidable egg vestments the spermatozoon must penetrate. Coordination of the rate of capacitation appropriate to fertilization in vivo may depend not only on the minimal time ordained for the species, but also on a heterogeneity among subpopulations of spermatozoa within any one sample and the timing of sperm transport to the oviduct.

Acrosome↗

Structure and evolutionary aspects of matrix metalloproteinases: a brief overview.

The matrix metalloproteinases (MMPs) are zinc dependent endopeptidases known for their ability to cleave one or several extracellular matrix (ECM) constituents, as well as non-matrix proteins. They comprise a large family of proteinases that share common structural and functional elements and are products of different genes. All members of this family contain a signal peptide, a propeptide and a catalytic domain. The catalytic domain contains two zinc ions and at least one calcium ion coordinated to various residues. All MMPs, with the exception matrilysin, have a hemopexin/vitronectin-like domain that is connected to the catalytic domain by a hinge or linker region. The hemopexin-like domain influences tissue inhibitor of metalloproteinases (TIMP) binding, the binding of certain substrates, membrane activation, and some proteolytic activities. It has been proposed that the origin of MMPs could be traced to before the emergence of vertebrates from invertebrates. It appears conceivable that the domain assemblies occurred at an early stage of the diversification of different MMPs and that they progressed through the evolutionary process independent of one another, and perhaps parallel to each other.

Amino Acid Sequence↗

Mitochondria and endoplasmic reticulum: the lethal interorganelle cross-talk.

The fundamental contribution of the mitochondria and ER to the decision made on the cell's fate has been increasingly recognized. This progress has illuminated the need for the mechanisms these organelles use to initiate and to propagate apoptotic signals. The toolbox of the mitochondria and ER is evolutionary conserved, overlapping and complementary. Furthermore, mitochondria are often closely associated with the ER providing the conditions for a local and privileged communication between the two organelles. The present review is concerned with the spatially and temporally coordinated utilization of Bcl-2 family proteins and Ca(2+) by the mitochondria and ER to control the membrane permeabilization in the mitochondria and to regulate Ca(2+) distribution and the activity of apoptotic proteins in the ER. The apoptotic means of the mitochondria and ER will eventually come together to control the dismantling of the cell by the caspases and other enzymes.

Animals↗

Isolation and characterization of four mouse ribosomal-protein-L18 genes that appear to be processed pseudogenes.

We describe the isolation and initial characterization of six independent lambda Charon 4A recombinant phages which carry four mouse genes for ribosomal protein L18 (L18-15, L18-17, L18-18, L18-30). Structural analysis indicates that these L18 genes contain the entire coding sequence (approx. 600 bp), but lack introns and differ both in their flanking and coding sequences. Based on these features we propose that these are processed pseudogenes. However, we have no indications whether these genes are expressed at either the transcriptional or translational levels. Quantitative estimation of sequence divergence of these genes suggest that the order of their evolutionary emergence (integration) is: first L18-17 and L18-18, then L18-15 and finally L18-30. We discuss the implication of the high proportion of L18 processed genes in this multigene family with respect to the coordinate regulation of r-proteins.

Animals↗

Coordinate regulation of drug metabolism by xenobiotic nuclear receptors: UGTs acting together with CYPs and glucuronide transporters.

Xenobiotic nuclear receptors (PXR, CAR, and the Ah receptor) coordinately induce genes involved in all phases of xenobiotic metabolism including oxidative metabolism, conjugation, and transport. The comment--dedicated to honor the memory of Herbert Remmer, mentor of the author K. W. B.--discusses mechanistic, functional, and evolutionary aspects of xenobiotic nuclear receptors which induce UGTs together with CYPs and glucuronide transporters in human and rodent liver and intestine. Recent findings on regulation of CYPs, UGTs, and transporters suggest that while nuclear receptor signaling induces different CYPs, regulation may converge on single UGTs and transporters. Functional consequences of co-regulation are discussed using examples from the metabolism of xeno- and endobiotics (drugs, bilirubin, bile salts, steroid hormones, and carcinogens). Animal-plant interactions may have been a major driving force in the evolutionary divergence of CYPs and UGTs in mammals and insects as well as in their regulation by nuclear receptors. In addition, regulation by nuclear receptors was probably shaped by the need for homeostatic control of endobiotic signals in the evolution of multicellular organisms.

Animals↗

Bioinorganic motifs: towards functional classification of metalloproteins.

UNLABELLED: The habitat of bioinorganic motifs (BIMs) is at the interface of biological inorganic chemistry and bioinformatics. BIM is defined as a common structural feature shared by functionally related, but not necessarily homologous, proteins, and consisting of the metal atom(s) and first coordination shell ligands. BIMs appear to be suitable for classification of metal centres at any level, from groups of unrelated proteins with similar function to different functional states of the same protein, and for description of possible evolutionary relationships of metalloproteins. However, they have not attracted wide attention from the bioinformatics community. Although their presence is appreciated, they are difficult to predict-therefore the current 'high-throughput' initiatives are likely to miss or ignore them altogether. The protein sequence databases do not distinguish between proteins containing different prosthetic groups (unless they have different sequences) or between apo- and holoprotein. On the other hand, the protein structure databases include data on 'hetero compounds' of various origin but these data are often inconsistent. A number of specialized databases dealing with BIMs and attempts to classify them are reviewed. SUPPLEMENTARY INFORMATION: The additional bibliography and list of Internet resources on bioinorganic chemistry are available at http://www.ebi.ac.uk/ approximately kirill/biometal/

Amino Acid Motifs↗

Stabilizing selection on behavior and morphology masks positive selection on the signal in a salamander pheromone signaling complex.

Natural selection maintains the integration and coordination of sets of phenotypic characters that collectively perform a task. In functional complexes in which characters span molecular to behavioral levels of organization, we might then expect similar modes of selection to produce similar patterns in evolutionary divergence at each level. To test this expectation, we diagnosed selection at behavioral, morphological, and molecular levels for courtship pheromone signaling by plethodontid salamanders. At the levels of morphology and behavior tens of millions of years of stasis (stabilizing selection) occur on each side of a transition from vaccination to olfactory delivery modes. As a proxy for the molecular level, we used plethodontid receptivity factor (PRF), a protein that is an active component of the pheromone. We cloned PRF from 12 Plethodon spp. spanning the delivery transition and obtained multiple alleles from each individual surveyed. Analyses of 61 alleles for PRF identified elevated nonsynonymous over synonymous substitution rates along lineages in a molecular phylogeny, and at 8% of sites in the protein, indicating that positive (directional) selection has acted on this vertebrate pheromone gene. Structural models showed PRF is in a family of cytokines characterized by a four-alpha-helix bundle. Positive selection in PRF was associated with receptor binding sites that are under purifying selection in other cytokines of that family. The evolutionary dynamics of the plethodontid pheromone delivery complex consists of stabilizing selection on morphological and behavioral aspects of signal delivery but positive selection on the signal mediated by receptors. Thus, different selection modes prevail at different levels in this reproductive functional complex. Evolutionary studies of integrated sets of characters therefore require separate analyses of selective action at each level.

Amino Acid Sequence↗

[Evolutionary significance of reciprocal biological effects of form and function using the example of the scapula in higher primates. 1].

The shoulder-blades of 99 catarrhine primates were investigated metrically and morphologically. In order to obtain comparable data, each analysed shoulder-blade was orientated in the same way in a 3-dimensional coordinate system. With the help of a diopthograph, the 3 planes were drawn without distorsion. On these planes the dimensions and angles were measured. These method produced the advantages of taking homologues data as well as of being able to compare the morphological data and its variability. Within the catarrhine primates, the area of the scapula (Fossa infra- and supraspinata) correlates highly significant with the body weight. Regarding the proportions and dimensions of the area of the scapula, there is no difference between the gibbons and the monkeys, regarding the dimensions, proportions and angles of the processes (acromion and coracoid) as well as the vertebral border of the scapula, the gibbons are close to the great apes. The areas of the shoulder-blades of the monkeys, where the shoulder stabilizing muscles originates, are fundamentally equal to each other. Whether body weight nor locomotion have an essential influence on its shape and structure (excl. Mandrillus). On the other hand, the variability of the joint area is considered and the processes are small. The gibbons, the great apes, and men are highly variable regarding the dimensions and the proportions of the area of the shoulder-blades. Regarding the dimensions, proportions, and angles of the acromion and the coracoid, where the shoulder joint stabilizing muscles originate, as well as the vertebral border, there are no fundamental differences between them and the processes are large and robuste.

Animals↗

Genetic and molecular analysis of Sn, a light-inducible, tissue specific regulatory gene in maize.

The Sn locus of maize is functionally similar to the R and B loci, in that Sn differentially controls the tissue-specific deposition of anthocyanin pigments in certain seedling and plant cells. We show that Sn shows molecular similarity to the R gene and have used R DNA probes to characterize several Sn alleles. Northern analysis demonstrates that all Sn alleles encode a 2.5 kb transcript, which is expressed in a tissue-specific fashion consistent with the distribution of anthocyanins. Expression of the Sn gene is light-regulated. However, the Sn: bol3 allele allows Sn mRNA transcription to occur in the dark, leading to pigmentation in dark-grown seedlings and cob integuments. We report the isolation of genomic and cDNA clones of the light-independent Sn: bol3 allele. Using Sn cDNA as a probe, the spatial and temporal expression of Sn has been examined. The cell-specific localization of Sn mRNA has been confirmed by in situ hybridization using labelled antisense RNA probes. According to its proposed regulatory role, expression of Sn precedes and, in turn, causes a coordinate and tissue-specific accumulation of mRNA of structural genes for pigment synthesis and deposition, such as A1 and C2. The functional and structural relationship between R, B, Lc and Sn is discussed in terms of an evolutionary derivation from a single ancestral gene which gave rise this diverse gene family by successive duplication events.

Acyltransferases↗

Coordinate regulation of the nuclear and plastidic genes coding for the subunits of the heteromeric acetyl-coenzyme A carboxylase.

Plastidic acetyl-coenzyme A (CoA) carboxylase (ACCase) catalyzes the first committed reaction of de novo fatty acid biosynthesis. This heteromeric enzyme is composed of one plastid-coded subunit (beta-carboxyltransferase) and three nuclear-coded subunits (biotin carboxy-carrier, biotin carboxylase, and alpha-carboxyltransferase). We report the primary structure of the Arabidopsis alpha-carboxyltransferase and beta-carboxyltransferase subunits deduced from nucleotide sequences of the respective genes and/or cDNA. Co-immunoprecipitation experiments confirm that the alpha-carboxyltransferase and beta-carboxyltransferase subunits are physically associated. The plant alpha-carboxyltransferases have gained a C-terminal domain relative to eubacteria, possibly via the evolutionary acquisition of a single exon. This C-terminal domain is divergent among plants and may have a structural function rather than being essential for catalysis. The four ACCase subunit mRNAs accumulate to the highest levels in tissues and cells that are actively synthesizing fatty acids, which are used either for membrane biogenesis in rapidly growing tissues or for oil accumulation in developing embryos. Development coordinately affects changes in the accumulation of the ACCase subunit mRNAs so that these four mRNAs maintain a constant molar stoichiometric ratio. These data indicate that the long-term, developmentally regulated expression of the heteromeric ACCase is in part controlled by a mechanism(s) that coordinately affects the steady-state concentrations of each subunit mRNA.

Acetyl-CoA Carboxylase↗

Evolution of the transferrin family: conservation of residues associated with iron and anion binding.

The transferrin family spans both vertebrates and invertebrates. It includes serum transferrin, ovotransferrin, lactoferrin, melanotransferrin, inhibitor of carbonic anhydrase, saxiphilin, the major yolk protein in sea urchins, the crayfish protein, pacifastin, and a protein from green algae. Most (but not all) contain two domains of around 340 residues, thought to have evolved from an ancient duplication event. For serum transferrin, ovotransferrin and lactoferrin each of the duplicated lobes binds one atom of Fe (III) and one carbonate anion. With a few notable exceptions each iron atom is coordinated to four conserved amino acid residues: an aspartic acid, two tyrosines, and a histidine, while anion binding is associated with an arginine and a threonine in close proximity. These six residues in each lobe were examined for their evolutionary conservation in the homologous N- and C-lobes of 82 complete transferrin sequences from 61 different species. Of the ligands in the N-lobe, the histidine ligand shows the most variability in sequence. Also, of note, four of the twelve insect transferrins have glutamic acid substituted for aspartic acid in the N-lobe (as seen in the bacterial ferric binding proteins). In addition, there is a wide spread substitution of lysine for the anion binding arginine in the N-lobe in many organisms including all of the fish, the sea squirt and many of the unusual family members i.e., saxiphilin and the green alga protein. It is hoped that this short analysis will provide the impetus to establish the true function of some of the TF family members that clearly lack the ability to bind iron in one or both lobes and additionally clarify the evolutionary history of this important family of proteins.

Animals↗

Synexpression groups in eukaryotes.

In 1960, Jacob and Monod described the bacterial operon, a cluster of functionally interacting genes whose expression is tightly coordinated. Global expression analysis has shown that the highly coordinate expression of genes functioning in common processes is also a widespread phenomenon in eukaryotes. These sets of co-regulated genes, or 'synexpression groups', show a striking parallel to the operon, and may be a key determinant facilitating evolutionary change leading to animal diversity.

Animals↗

Is there an evolutionary mismatch between the normal physiology of the human dopaminergic system and current environmental conditions in industrialized countries?

A large body of evidence has recently defined a field theory known as 'evolutionary mismatch', which derives its attributes largely from the fact that current environmental conditions are completely different from those in which the human central nervous system evolved. Current views on the evolutionary mismatch theory lack, however, any attempts to define which brain areas or neuronal circuits should be mostly involved in coding such misevolved traits and to what extent our neurobiological knowledge can be applied to the topographical localization of a specific psychopathology. In this respect the mesocorticolimbic dopaminergic circuits have long been misconceptualized as simple reward or reinforcement systems. Instead, they motivate and coordinate the functions of the higher brain areas that mediate planning and foresight and direct finalized movement in both animals and humans. These systems make animals intensely interested in exploring the world around them, but by the same means they also make them susceptible to the environmental stimuli that have been sought and consumed. It is has been speculated that the cortical dopamine targets that developed most recently in phylogeny are of particular functional value, and that the mesocorticolimbic dopaminergic system is involved in more complex integrative functions than previously assumed. In the present paper I will argue that some mental disorders may have their deep roots in the evolutionary mismatch between the normal physiology of the mesocorticolimbic dopaminergic system and the current environmental conditions in affluent societies.

Animals↗

Integrative processing: a biological foundation for psychotherapy.

The biological base for psychodynamic psychotherapy has been increasingly recognized as archaic--unable to provide a conceptual framework within which to place the rapid progress in the basic neurosciences and the clinical successes of modern psychopharmacology. A gradual conceptual synthesis has been occurring between the study of the formal properties of general systems, including both animate and inanimate systems and evolutionary thinking, with special emphasis on the adaptive design of the human mind/brain. That synthesis points the way to an evolutionary-based complex adaptive systems model. Such a model would reflect our understanding of the brain as a modular system, with distributed memory and no central locus of executive control. A prominent design feature would be an automatically operating process coordinating and harmonizing various specialized brain modules--integrative processing. Pennebaker's research (Opening Up: The Healing Power of Expressing Emotions, Guilford, 1997) on personal self-disclosure illustrates ways in which the concept of integrative processing can help our understanding of the brain's basic function in dealing with emotional issues. It also provides a useful way of conceptualizing the clinical effect of psychopharmacological interventions.

Adaptation, Physiological↗

Orthogenesis of the hominids: an exploration using biorthogonal grids.

In 1917, D'Arch Thompson suggested that one should study the change from one biological form to another by examining the unique mathematical object that maps between them in accord with biological homologies. Biorthogonal grids provide a particular coordinate system for visualizing such a map and lead to a quantitative syntax in which a change in shape is reduced to differential changes in size. Application of the method to hominid skull phylogeny has demonstrated three principal axes of evolutionary change anatomically homologous over a fossil sequence.

Animals↗

Development of guidelines for design and construction of hospitals and health care facilities.

The Guidelines for Design and Construction of Hospitals and Health Care Facilities is the most widely referred to design document in the USA and is influential throughout the world. The Facility Guidelines Institute (FGI) was founded to provide continuity in the guidelines revision process. FGI functions as a contractual, fundraising, and coordinating entity to develop and enhance the content and format of guidelines publications and of ancillary services that encourage and improve their application and use. The Guidelines and the methodology for revising them have been, and still are, in an evolutionary process. It is the desire of the AIA/AAH and FGI to see that the process continues to change and improve with each passing cycle.

Academies and Institutes↗