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PubMed1996

Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T cell stimulatory capacity: T-T help via APC activation.

We investigated the possibility that T helper cells might enhance the stimulatory function of dendritic cells (DCs). We found that ligation of CD40 by CD40L triggers the production of extremely high levels of bioactive IL-12. Other stimuli such as microbial agents, TNF-alpha or LPS are much less effective or not at all. In addition, CD40L is the most potent stimulus in upregulating the expression of ICAM-1, CD80, and CD86 molecules on DCs. These effects of CD40 ligation result in an increased capacity of DCs to trigger proliferative responses and IFN-gamma production by T cells. These findings reveal a new role for CD40-CD40L interaction in regulating DC function and are relevant to design therapeutic strategies using cultured DCs.

Antigen-Presenting Cells↗

PubMed1985

Pressate from peat dewatering as a substrate for bacterial growth.

This study considered the possibility of using water expressed during the drying of fuel-grade peat as a substrate for microbial growth. Highly humified peat pressed for 2.5 min at 1.96 MPa produced water with a chemical oxygen demand of 690 mg/liter. Several biological compounds could be produced by using the organic matter in expressed peat water as a substrate. These included polymers such as chitosan, contained in the cell wall of Rhizopus arrhizus, and two extracellular polysaccharides, xanthan gum and pullulan, produced by Xanthomonas campestris and Aureobasidium pullulans, respectively. A very effective surfactant was produced by Bacillus subtilis grown in the expressed water. Small additions of nutrients to the peat pressate were necessary to obtain substantial yields of products. The addition of peptone, yeast extract, and glucose improved production of the various compounds. Biological treatment improved the quality of the expressed water to the extent that in an industrial process it could be returned to the environment.

Journal Article↗

PubMed1994

Coliform counts and Escherichia coli in raw commercial milk from dairy farmers in Kiambu District, Kenya.

The rate of contamination with coliforms and incidence of Escherichia coli (E. coli) in raw milk supplied by farmers to dairy cooperative societies for marketing was investigated. About forty two (42.2%) percent of the milk samples from farmers cans and 10.3% of samples from cooperative cans were found to be free of coliforms, while 89.5% of the samples from farmers cans and 50% samples from cooperative cans could be considered to be of good quality with no more than 50,000 coliforms/ml of milk. Forty two E. coli strains were isolated from milk samples, five of which were found to be enteropathogenic, while none was found to be of serogroup O157. The results indicated that a good number of farmers draw milk under satisfactory conditions, but awareness campaigns on clean milking, milk handling and storage practices should be stepped up in order to reach farmers who may not be informed. Again the study showed that raw milk can get contaminated with enteropathogenic strains of E. coli that can pose a potential risk to humans, thus calling for extra care when preparing milk and milk products that are to be consumed by human beings.

Animals↗

PubMed2002

Re-annotation of genome microbial coding-sequences: finding new genes and inaccurately annotated genes.

BACKGROUND: Analysis of any newly sequenced bacterial genome starts with the identification of protein-coding genes. Despite the accumulation of multiple complete genome sequences, which provide useful comparisons with close relatives among other organisms during the annotation process, accurate gene prediction remains quite difficult. A major reason for this situation is that genes are tightly packed in prokaryotes, resulting in frequent overlap. Thus, detection of translation initiation sites and/or selection of the correct coding regions remain difficult unless appropriate biological knowledge (about the structure of a gene) is imbedded in the approach. RESULTS: We have developed a new program that automatically identifies biologically significant candidate genes in a bacterial genome. Twenty-six complete prokaryotic genomes were analyzed using this tool, and the accuracy of gene finding was assessed by comparison with existing annotations. This analysis revealed that, despite the enormous effort of genome program annotators, a small but not negligible number of genes annotated within the framework of sequencing projects are likely to be partially inaccurate or plainly wrong. Moreover, the analysis of several putative new genes shows that, as expected, many short genes have escaped annotation. In most cases, these new genes revealed frameshifts that could be either artifacts or genuine frameshifts. Some entirely unexpected new genes have also been identified. This allowed us to get a more complete picture of prokaryotic genomes. The results of this procedure are progressively integrated into the SWISS-PROT reference databank. CONCLUSIONS: The results described in the present study show that our procedure is very satisfactory in terms of gene finding accuracy. Except in few cases, discrepancies between our results and annotations provided by individual authors can be accounted for by the nature of each annotation process or by specific characteristics of some genomes. This stresses that close cooperation between scientists, regular update and curation of the findings in databases are clearly required to reduce the level of errors in genome annotation (and hence in reducing the unfortunate spreading of errors through centralized data libraries).

Computational Biology↗

PubMed2005

Apigenin and tt-farnesol with fluoride effects on S. mutans biofilms and dental caries.

Apigenin (Api) and tt-farnesol (Far) are two naturally occurring agents that affect the development of cariogenic biofilms. Fluoride (F) interferes physicochemically with caries development and also exhibits antibacterial activity. We examined whether the association of Api and Far enhance the anti-caries properties of F by acting cooperatively on the expression of virulence of Streptococcus mutans. The biological effects of each of the agents were greatly enhanced when used in combination with F. In general, biofilms treated with Api and/or Far in combination with F displayed less biomass and fewer insoluble glucans and iodophilic polysaccharides than did those treated with the test agents alone (P < 0.05). The combination of the test agents with F was highly effective in preventing caries development in rats, especially Api+Far+F, and results were comparable with those observed with chlorhexidine + F (positive control). Results from these studies showed that apigenin and tt-farnesol may enhance the cariostatic effectiveness of fluoride.

Animals↗

PubMed2003

Standards of the in vitro mutation frequency study and the antimicrobial activity study in gut.

In view of the recent rapid increase in incidence of infection with antimicrobial resistant bacteria in human medicine, there is international controversy as to the medical risk that is created by transfer of antimicrobial resistant bacteria and antimicrobial resistant genes, which may be produced through the processes of administration of antimicrobials to food-producing animals, via the food chain. Accordingly, International Cooperation on Harmonization of Technical Requirements for Registration of Veterinary Medicinal Products (VICH) provides the comprehensive guidelines for characterizing selection of antimicrobial resistance by bacteria which may adversely affect human health in order to establish the system of registry of antimicrobial drugs to be administered to food- producing animals. Currently, Japanese Society of Antimicrobials for Animals recognizes the lack of technical test standards in compliance with VICH guidelines in the world and has established the test standards for "in vitro mutation frequency studies" to evaluate the appearance frequency and resistant level of resistant bacteria and those for studies on the "antimicrobial activity in gut" to estimate the effects on intestinal flora from professional aspects.

Animal Husbandry↗

PubMed1999

Differential scanning calorimetric study of the effect of the antimicrobial peptide gramicidin S on the thermotropic phase behavior of phosphatidylcholine, phosphatidylethanolamine and phosphatidylglycerol lipid bilayer membranes.

We have studied the effects of the antimicrobial peptide gramicidin S (GS) on the thermotropic phase behavior of large multilamellar vesicles of dimyristoylphosphatidylcholine (DMPC), dimyristoylphosphatidylethanolamine (DMPE) and dimyristoyl phosphatidylglycerol (DMPG) by high-sensitivity differential scanning calorimetry. We find that the effect of GS on the lamellar gel to liquid-crystalline phase transition of these phospholipids varies markedly with the structure and charge of their polar headgroups. Specifically, the presence of even large quantities of GS has essentially no effect on the main phase transition of zwitterionic DMPE vesicles, even after repeating cycling through the phase transition, unless these vesicles are exposed to high temperatures, after which a small reduction in the temperature, enthalpy and cooperativity of the gel to liquid-crystalline phase transitions is observed. Similarly, even large amounts of GS produce similar modest decreases in the temperature, enthalpy and cooperativity of the main phase transition of DMPC vesicles, although the pretransition is abolished at low peptide concentrations. However, exposure to high temperatures is not required for these effects of GS on DMPC bilayers to be manifested. In contrast, GS has a much greater effect on the thermotropic phase behavior of anionic DMPG vesicles, substantially reducing the temperature, enthalpy and cooperativity of the main phase transition at higher peptide concentrations, and abolishing the pretransition at lower peptide concentrations as compared to DMPC. Moreover, the relatively larger effects of GS on the thermotropic phase behavior of DMPG vesicles are also manifest without cycling through the phase transition or exposure to high temperatures. Furthermore, the addition of GS to DMPG vesicles protects the phospholipid molecules from the chemical hydrolysis induced by their repeated exposure to high temperatures. These results indicate that GS interacts more strongly with anionic than with zwitterionic phospholipid bilayers, probably because of the more favorable net attractive electrostatic interactions between the positively charged peptide and the negatively charged polar headgroup in such systems. Moreover, at comparable reduced temperatures, GS appears to interact more strongly with zwitterionic DMPC than with zwitterionic DMPE bilayers, probably because of the more fluid character of the former system. In addition, the general effects of GS on the thermotropic phase behavior of zwitterionic and anionic phospholipids suggest that it is located at the polar/apolar interface of liquid-crystalline bilayers, where it interacts primarily with the polar headgroup and glycerol-backbone regions of the phospholipid molecules and only secondarily with the lipid hydrocarbon chains. Finally, the considerable lipid specificity of GS interactions with phospholipid bilayers may prove useful in the design of peptide analogs with stronger interactions with microbial as opposed to eucaryotic membrane lipids.

Anti-Infective Agents↗

PubMed1995

Capacity for methane oxidation in landfill cover soils measured in laboratory-scale soil microcosms.

Laboratory-scale soil microcosms containing different soils were permeated with CH(inf4) for up to 6 months to investigate their capacity to develop a methanotrophic community. Methane emissions were monitored continuously until steady states were established. The porous, coarse sand soil developed the greatest methanotrophic capacity (10.4 mol of CH(inf4) (middot) m(sup-2) (middot) day(sup-1)), the greatest yet reported in the literature. Vertical profiles of O(inf2), CH(inf4), and methanotrophic potential in the soils were determined at steady state. Methane oxidation potentials were greatest where the vertical profiles of O(inf2) and CH(inf4) overlapped. A significant increase in the organic matter content of the soil, presumably derived from methanotroph biomass, occurred where CH(inf4) oxidation was greatest. Methane oxidation kinetics showed that a soil community with a low methanotrophic capacity (V(infmax) of 258 nmol (middot) g of soil(sup-1) (middot) h(sup-1)) but relatively high affinity (k(infapp) of 1.6 (mu)M) remained in N(inf2)-purged control microcosms, even after 6 months without CH(inf4). We attribute this to a facultative, possibly mixotrophic, methanotrophic microbial community. When purged with CH(inf4), a different methanotrophic community developed which had a lower affinity (k(infapp) of 31.7 (mu)M) for CH(inf4) but a greater capacity (V(infmax) of 998 nmol (middot) g of soil(sup-1) (middot) h(sup-1)) for CH(inf4) oxidation, reflecting the enrichment of an active high-capacity methanotrophic community. Compared with the unamended control soil, amendment of the coarse sand with sewage sludge enhanced CH(inf4) oxidation capacity by 26%; K(inf2)HPO(inf4) amendment had no significant effect, while amendment with NH(inf4)NO(inf3) reduced the CH(inf4) oxidation capacity by 64%. In vitro experiments suggested that NH(inf4)NO(inf3) additions (10 and 71 (mu)mol (middot) g of soil(sup-1)) inhibited CH(inf4) oxidation by a nonspecific ionic effect rather than by specific inhibition by NH(inf4)(sup+).

Journal Article↗

PubMed1996

Cleavage of human complement component C5 by cysteine proteinases from Porphyromonas (Bacteroides) gingivalis. Prior oxidation of C5 augments proteinase digestion of C5.

Since severe periodontitis is characterized by an acute inflammatory response with cellular infiltration and microbial overgrowth, plasma proteins could be exposed to both proteinases and oxidants released from the granulocytes, as well as to proteinases from the microorganisms. When human complement component C5 was digested by cysteine proteinases (i.e. gingipain-R and gingipain-K) from Porphyromonas gingivalis, limited cleavage of the C5 molecule was observed. If C5 was first oxidized by hydroxyl radicals, these gingipains converted modified C5 to fragments that exhibited significantly greater pro-inflammatory activity than did digests of unmodified C5. After cleavage of oxidized C5 by gingipain-R, the digest exhibited measurably greater neutrophil enzyme release and chemotaxis of human polymorphonuclear leukocytes (PMNs) compared with the activities of unoxidized C5 digests. Gingipain-K generates virtually no polarization or chemotactic activity of human PMNs from C5, nor is enzyme release stimulated by these C5 digests. However, when oxidized C5 was digested by gingipain-K, human PMNs were stimulated for polarization, chemotaxis and enzyme release indicating that an active fragment had been generated. Proteolysis of oxidized C5 evokes greater neutrophil activation than does proteolysis of unoxidized protein, a fact which supports the hypothesis that oxidation and proteolysis may be coupled to enhance the destructive effects of the inflammatory process. These results, in which digests of both oxidized and unmodified complement component C5 were evaluated, support the general concept that oxidation and proteolysis may participate cooperatively in amplifying both the severity and duration of the inflammatory reaction.

Adhesins, Bacterial↗

PubMed2000

Inhibition of the Staphylococcus aureus NADPH-dependent enoyl-acyl carrier protein reductase by triclosan and hexachlorophene.

Enoyl-acyl carrier protein reductase (FabI) plays a determinant role in completing cycles of elongation in type II fatty acid synthase systems and is an important target for antibacterial drugs. The FabI component of Staphylococcus aureus (saFabI) was identified, and its properties were compared with Escherichia coli FabI (ecFabI). ecFabI and saFabI had similar specific activities, and saFabI expression complemented the E. coli fabI(Ts) mutant, illustrating that the Gram-positive FabI was interchangeable with the Gram-negative FabI enzyme. However, ecFabI was specific for NADH, whereas saFabI exhibited specific and positive cooperative binding of NADPH. Triclosan and hexachlorophene inhibited both ecFabI and saFabI. The triclosan-resistant ecFabI(G93V) protein was also refractory to hexachlorophene inhibition, illustrating that both drugs bind at the FabI active site. Both the introduction of a plasmid expressing the safabI gene or a missense mutation in the chromosomal safabI gene led to triclosan resistance in S. aureus; however, these strains did not exhibit cross-resistance to hexachlorophene. The replacement of the ether linkage in triclosan by a carbon bridge in hexachlorophene prevented the formation of a stable FabI-NAD(P)(+)-drug ternary complex. Thus, the formation of this ternary complex is a key determinant of the antibacterial activity of FabI inhibitors.

Amino Acid Sequence↗

PubMed1982

Microbial flora of the mouse ileum mucous layer and epithelial surface.

We have developed new methods to minimize fluid shear during preparation of specimens for electron microscopy and to retain the mucous blanket that covers the tissue surface of the ileum in mice. We also used general stabilization by nonspecific antibodies to minimize the collapse of the mucous layer during dehydration for electron microscopy. These methods allowed us to visualize the gradual progression of the mucous blanket from a thin diaphanous layer in newborn animals to a very thick (ca. 50 micrometers), coherent structure in older animals that contained a mixed population of bacteria and protozoa. Some bacteria, notably filamentous forms, were patently anchored to the epithelial tissue but projected into the mucous blanket, whereas others clearly existed within the mucous blanket and were unattached to the epithelial surface. Similarly, some protozoa were firmly attached to the tissue surface, whereas others were suspended in the viscous mucous blanket. In an adult animal, the mucous blanket was a very thick layer which actually occluded most of the tissue surface and contained a rich variety of bacteria and protozoa.

Animals↗

PubMed2025

Two decades of resistance surveillance by the British Society for Antimicrobial Chemotherapy: design, development, delivery, deficiencies and future directions.

The British Society for Antimicrobial Chemotherapy Antimicrobial Surveillance Project was established in the United Kingdom (UK) and Ireland in response to dissatisfaction with existing antimicrobial surveillance which, in the 1990s, was fragmented and poorly informative for clinical and public heath purposes. The model developed into an integrated Project that was novel in its management and financing, being a true collaboration between a medical charity, pharmaceutical companies and the laboratories contracted to perform the testing. Separate 'Programmes' within an overall 'Project' collected and tested community- and hospital-acquired respiratory and bloodstream infection isolates. Cooperation with public sector bodies allowed data collection from the Project to be compared to routinely collected data from National Health Service laboratories. Between 1999 and 2019 the Project delivered test results on almost 100 000 isolates, from 17 bacterial genera to 44 antimicrobial agents. The results were made available annually on a specially constructed web site. In this supplement, we summarize the data collected in a series of papers relevant to the two programmes, discussing the Project's strengths and deficiencies. Support for the Project declined in the period after 2010, and collection ceased after 20 years, its demise related to changing priorities within the partner organizations. However, the bacterial collection remains and is to be maintained to assist in future work in combating antimicrobial resistance.

United Kingdom↗

PubMed1986

Antibiotic-resistant isolates of Streptococcus pneumoniae from clinical specimens: a cluster of serotype 19A organisms in Brooklyn, New York.

Ten of 294 isolates of Streptococcus pneumoniae from patients enrolled in a Veterans Administration Cooperative Studies Program trial of pneumococcal vaccine efficacy were moderately resistant or resistant to penicillin. Nine of these organisms were serotype 19A isolated from patients at the Brooklyn (New York) V.A. Medical Center over an 18-month period (March 1983-November 1984). The minimal inhibitory concentration of penicillin for these pneumococci ranged from 1.0 to 2.0 micrograms/ml by the agar dilution technique and from 4.0 to 8.0 micrograms/ml by tube dilution. These organisms were resistant also to other beta-lactam antibiotics and to tetracycline, chloramphenicol, and trimethoprim-sulfamethoxazole. They were sensitive to erythromycin, clindamycin, vancomycin, and rifampin. The epidemiological source of these isolates was not discovered. However, it is possible that a focus of multiple antibiotic-resistant serotype 19A S. pneumoniae is present in Brooklyn.

Drug Resistance, Microbial↗

PubMed2005

Monitoring global rates of biodiversity change: challenges that arise in meeting the Convention on Biological Diversity (CBD) 2010 goals.

By agreeing to strive for 'a significant reduction in the current rate of loss of biological diversity' by the year 2010, political leaders at the 2002 World Summit on Sustainable Development (held in Johannesburg, South Africa) presented conservation scientists with a great opportunity, but also one of their most significant challenges. This is an extremely exciting and laudable development, but this reporting process could be made yet more powerful if it incorporates, from the outset, independent scientific assessment of the measures, how they are analysed, and practical ways of plugging key gaps. This input is crucial if the measures are to be widely owned, credible and robust to the vigorous external scrutiny to which they will doubtless be exposed. Assessing how rates of biodiversity loss have changed from current levels by 2010 will require that a given attribute has been measured at least three times; however, most habitats, species, populations and ecosystem services have not been assessed even once. Furthermore, the best data on which to base estimates of biodiversity loss are biased towards the charismatic vertebrate species; unfortunately, these supply minimal services to the human economy. We have to find ways to redress this taxonomic imbalance and expand our analyses to consider the vast diversity of invertebrate, fungal and microbial species that play a role in determining human health and economic welfare. In the first part of this paper I will use examples from local and regional monitoring of biological diversity to examine the desired properties of 'ideal indicators'. I will then change focus and examine an initial framework that asks how we might monitor changes in the economic goods and services provided by natural ecosystems. I will use this exercise to examine how the set of possible indicators given by the Convention on Biological Diversity might be modified in ways that provide a more critical assay of the economic value of biological diversity. Here I will emphasize that we need not only to monitor these benefits, but also to significantly increase public awareness of human dependence upon the role that non-voting species play in driving the world's financial economy.

Biodiversity↗

PubMed1978

Veterans Administration Cooperative Study on Bowel Preparation for Elective Colorectal Operations: impact of oral antibiotic regimen on colonic flora, wound irrigation cultures and bacteriology of septic complications.

A ten hospital cooperative study comparing prophylactic oral neomycin and erythromycin base versus placebo demonstrated clinical efficacy of the antibiotics in preventing septic complications following elective colon operations. The present report concerns microbiological studies accomplished during this trial. Cultures of colon contents during surgery showed the antibiotic prep reduced concentrations of both aerobes and anaerobes by approximately 10(5) bacteria/ml. Virtually all major bacterial components of the normal flora were affected. Wound irrigation specimens at the time of closure failed to predict subsequent wound infection, but significantly fewer antibiotic recipients had positive irrigation cultures. Postoperative stool specimens showed that the oral antibiotics did not cause an emergence in resistant forms. Bacteriological studies of postoperative infections indicated that most postoperative infections involved a mixed aerobic-anaerobic flora, and that Bacteroides fragilis accounted for six of eight episodes of bacteremia.

Bacteria↗

PubMed2005

Effects of different soil types on the Collembolans Folsomia candida and Hypogastrura assimilis using the herbicide Phenmedipham.

Soil ecotoxicology studies are usually performed in standard soils such as Organization for Economic Cooperation and Development artificial soil or LUFA ST. 2.2, a natural soil. When assessing the toxic effects in the environment, soil properties are often different from those in standard soils, which might lead to different exposure situation for the test species and therefore to misleading conclusions. Selected to cover a broad range of properties and based on the Euro-Soils concept, 17 different soils were studied regarding their suitability to two tes species: Folsomia candida and Hypogastrura assimilis (Collembola). In reproduction tests, the test species reacted differently to the soils. F. candida was less affected by soil properties: 500 to 1200 juveniles/vessel were found in untreated soils (i.e. controls). These differences can be attributed to normal interindividual variability. H. assimilis showed a significant correlation with maximum water-holding capacity and also a tendency to lower the reproductive output in soils with a low pH (<4). Therefore, some soils were revealed to be inappropriate for tests with H. assimilis. In the main tests, the effect of the reference test substance Phenmedipham (formulation Betosyp) was studied in those soils where sufficient reproduction was determined beforehand. Clearly, the chronic end point was more sensitive than survival when testing Phenmedipham. In H. assimilis, because of high variability and low effects of tested dosages, no conclusions could be drawn. In F. candida, different soils caused different toxic effects: Juveniles preferred soils with high C-to-N ratios. Higher microbial activity might support a quicker metabolization of the test substance. In general, the toxic response is caused by a synergistic action of several soil properties with each of them exerting an effect too small to be clarified with the available set of data.

Animals↗

PubMed1998

Analysis of bacterial meningitis during 1992-1996 in Poland.

Retrospective study of bacterial meningitis cases was performed by analysis of filled questionnaires received from 38 different hospitals located in 27 out of 49 provinces of Poland. Obtained data allowed to indicate that S. epidermidis, N. meningitidis, S. pneumoniae and H. influenzae were the most common bacterial strains isolated from cerebrospinal fluid of meningitis patients during the last five years. Besides data analysis performed, some strains of N. meningitidis (n = 97), H. influenzae (n = 28) and S. pneumoniae (n = 39) isolated from cerebrospinal fluid of meningitis patients hospitalized in different places in Poland sent by cooperating hospital laboratories (1995-1996), were phenotypically characterized. Neisseria meningitidis B:22:P1.14 was the most common isolate phenotype during the investigated time period. Streptococcus pneumoniae of twenty different serological types were isolated. Type 1 was the dominant--18% of strains. All but one Haemophilus influenzae strains isolated from cerebrospinal fluid belonged to serological type b. Biotyping showed presence of only two types: I and II, 39.3% and 60.7% of isolates respectively. The sensitivity of collected strains to selected antimicrobial agents (penicillin, cefotaxime, ceftriaxone, sulphametoxazol, chloramphenicol, tetracycline, ciprofloxacin, rifampin and erythromycin) used in treatment and prophylaxis of bacterial meningitis was investigated. Minimum inhibitory concentrations were determined by agar dilution method or with the use of E-tests. All investigated strains but one N. meningitidis, were not resistant to penicillin (MIC < or = 1 microgram/ml).

Adolescent↗

PubMed2000

Solution structure of PCP, a prototype for the peptidyl carrier domains of modular peptide synthetases.

BACKGROUND: Nonribosomal peptide synthetases (NRPSs) are large modular enzymes responsible for the synthesis of a variety of microbial bioactive peptides. They consist of modules that each recognise and incorporate one specific amino acid into the peptide product. A module comprises several domains, which carry out the individual reaction steps. After activation by the adenylation domain, the amino acid substrate is covalently tethered to a 4'-phosphopantetheinyl cofactor of a peptidyl carrier domain (PCP) that passes the substrate to the reaction centres of the consecutive domains. RESULTS: The solution structure of PCP, a distinct peptidyl carrier protein derived from the equivalent domain of an NRPS, was solved using NMR techniques. PCP is a distorted four-helix bundle with an extended loop between the first two helices. Its overall fold resembles the topology of acyl carrier proteins (ACPs) from Escherichia coli fatty acid synthase and actinorhodin polyketide synthase from Streptomyces coelicolor; however, the surface polarity and the length and relative alignment of the helices are different. The conserved serine, which is the cofactor-binding site, has the same location as in the ACPs and is situated within a stretch of seven flexible residues. CONCLUSIONS: The structure of PCP reflects its character as a protein domain. The fold is well defined between residues 8 and 82 and the structural core of the PCP domain can now be defined as a region spanning 37 amino acids in both directions from the conserved serine. The flexibility of the post-translationally modified site might have implications for interactions with the cooperating proteins or NRPS domains.

Amino Acid Sequence↗