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| - | [[Image:2c5w.gif|left|200px]] | + | {{Seed}} |
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| | {{STRUCTURE_2c5w| PDB=2c5w | SCENE= }} | | {{STRUCTURE_2c5w| PDB=2c5w | SCENE= }} |
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| - | '''PENICILLIN-BINDING PROTEIN 1A (PBP-1A) ACYL-ENZYME COMPLEX (CEFOTAXIME) FROM STREPTOCOCCUS PNEUMONIAE'''
| + | ===PENICILLIN-BINDING PROTEIN 1A (PBP-1A) ACYL-ENZYME COMPLEX (CEFOTAXIME) FROM STREPTOCOCCUS PNEUMONIAE=== |
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| - | ==Overview==
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| - | Streptococcus pneumoniae is a major human pathogen whose infections have been treated with beta-lactam antibiotics for over 60 years, but the proliferation of strains that are highly resistant to such drugs is a problem of worldwide concern. Beta-lactams target penicillin-binding proteins (PBPs), membrane-associated enzymes that play essential roles in the peptidoglycan biosynthetic process. Bifunctional PBPs catalyze both the polymerization of glycan chains (glycosyltransfer) and the cross-linking of adjacent pentapeptides (transpeptidation), while monofunctional enzymes catalyze only the latter reaction. Although S. pneumoniae has six PBPs, only three (PBP1a, PBP2x, PBP2b) are major resistance determinants, with PBP1a being the only bifunctional enzyme. PBP1a plays a key role in septum formation during the cell division cycle and its modification is essential for the development of high-level resistance to penicillins and cephalosporins. The crystal structure of a soluble form of pneumococcal PBP1a (PBP1a*) has been solved to 2.6A and reveals that it folds into three domains. The N terminus contains a peptide from the glycosyltransfer domain bound to an interdomain linker region, followed by a central, transpeptidase domain, and a small C-terminal unit. An analysis of PBP1a sequences from drug-resistant clinical strains in light of the structure reveals the existence of a mutational hotspot at the entrance of the catalytic cleft that leads to the modification of the polarity and accessibility of the mutated PBP1a active site. The presence of this hotspot in all variants sequenced to date is of key relevance for the development of novel antibiotherapies for the treatment of beta-lactam-resistant pneumococcal strains.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_16316661}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 16316661 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_16316661}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Penicillin-binding]] | | [[Category: Penicillin-binding]] |
| | [[Category: Peptidoglycan synthesis]] | | [[Category: Peptidoglycan synthesis]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 21:17:59 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 21:02:09 2008'' |
Revision as of 18:02, 27 July 2008
Template:STRUCTURE 2c5w
PENICILLIN-BINDING PROTEIN 1A (PBP-1A) ACYL-ENZYME COMPLEX (CEFOTAXIME) FROM STREPTOCOCCUS PNEUMONIAE
Template:ABSTRACT PUBMED 16316661
About this Structure
2C5W is a Protein complex structure of sequences from Streptococcus pneumoniae. Full crystallographic information is available from OCA.
Reference
Crystal structure of penicillin-binding protein 1a (PBP1a) reveals a mutational hotspot implicated in beta-lactam resistance in Streptococcus pneumoniae., Contreras-Martel C, Job V, Di Guilmi AM, Vernet T, Dideberg O, Dessen A, J Mol Biol. 2006 Jan 27;355(4):684-96. Epub 2005 Nov 9. PMID:16316661
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