2c5w

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[[Image:2c5w.gif|left|200px]]<br />
 
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<applet load="2c5w" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="2c5w, resolution 2.55&Aring;" />
 
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'''PENICILLIN-BINDING PROTEIN 1A (PBP-1A) ACYL-ENZYME COMPLEX (CEFOTAXIME) FROM STREPTOCOCCUS PNEUMONIAE'''<br />
 
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==Overview==
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==PENICILLIN-BINDING PROTEIN 1A (PBP-1A) ACYL-ENZYME COMPLEX (CEFOTAXIME) FROM STREPTOCOCCUS PNEUMONIAE==
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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.
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<StructureSection load='2c5w' size='340' side='right'caption='[[2c5w]], [[Resolution|resolution]] 2.55&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2c5w]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptococcus_pneumoniae_R6 Streptococcus pneumoniae R6]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2C5W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2C5W FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.55&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CEF:CEFOTAXIME,+C3+CLEAVED,+OPEN,+BOUND+FORM'>CEF</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2c5w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2c5w OCA], [https://pdbe.org/2c5w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2c5w RCSB], [https://www.ebi.ac.uk/pdbsum/2c5w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2c5w ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/PBPA_STRR6 PBPA_STRR6] Cell wall formation.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/c5/2c5w_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2c5w ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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==About this Structure==
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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<ref>PMID:16316661</ref>
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2C5W is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Streptococcus_pneumoniae Streptococcus pneumoniae] with ZN, CL, EDO and PCZ as [http://en.wikipedia.org/wiki/ligands ligands]. Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2C5W OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16316661 16316661]
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</div>
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[[Category: Protein complex]]
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<div class="pdbe-citations 2c5w" style="background-color:#fffaf0;"></div>
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[[Category: Streptococcus pneumoniae]]
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[[Category: Contreras-Martel, C.]]
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[[Category: Dessen, A.]]
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[[Category: Dideberg, O.]]
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[[Category: Guilmi, A.M.Di.]]
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[[Category: Job, V.]]
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[[Category: Vernet, T.]]
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[[Category: CL]]
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[[Category: EDO]]
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[[Category: PCZ]]
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[[Category: ZN]]
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[[Category: antibiotic resistance]]
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[[Category: cell shape]]
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[[Category: cell wall]]
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[[Category: multifunctional enzyme]]
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[[Category: penicillin-binding]]
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[[Category: peptidoglycan synthesis]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 17:59:50 2007''
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==See Also==
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*[[Penicillin-binding protein 3D structures|Penicillin-binding protein 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
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[[Category: Streptococcus pneumoniae R6]]
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[[Category: Contreras-Martel C]]
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[[Category: Dessen A]]
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[[Category: Di Guilmi A-M]]
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[[Category: Dideberg O]]
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[[Category: Job V]]
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[[Category: Vernet T]]

Current revision

PENICILLIN-BINDING PROTEIN 1A (PBP-1A) ACYL-ENZYME COMPLEX (CEFOTAXIME) FROM STREPTOCOCCUS PNEUMONIAE

PDB ID 2c5w

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