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3zg5

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==Crystal structure of PBP2a from MRSA in complex with peptidoglycan analogue at allosteric==
==Crystal structure of PBP2a from MRSA in complex with peptidoglycan analogue at allosteric==
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<StructureSection load='3zg5' size='340' side='right' caption='[[3zg5]], [[Resolution|resolution]] 2.55&Aring;' scene=''>
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<StructureSection load='3zg5' size='340' side='right'caption='[[3zg5]], [[Resolution|resolution]] 2.55&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[3zg5]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZG5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ZG5 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[3zg5]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus_subsp._aureus_Mu50 Staphylococcus aureus subsp. aureus Mu50] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZG5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZG5 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
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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='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=AMV:METHYL+2-(ACETYLAMINO)-3-O-[(1R)-1-CARBOXYETHYL]-2-DEOXY-BETA-D-GLUCOPYRANOSIDE'>AMV</scene>, <scene name='pdbligand=DAL:D-ALANINE'>DAL</scene>, <scene name='pdbligand=FGA:GAMMA-D-GLUTAMIC+ACID'>FGA</scene></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=AMV:METHYL+2-(ACETYLAMINO)-3-O-[(1R)-1-CARBOXYETHYL]-2-DEOXY-BETA-D-GLUCOPYRANOSIDE'>AMV</scene>, <scene name='pdbligand=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DAL:D-ALANINE'>DAL</scene>, <scene name='pdbligand=FGA:GAMMA-D-GLUTAMIC+ACID'>FGA</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3zfz|3zfz]], [[3zg0|3zg0]], [[3zh3|3zh3]], [[3zh4|3zh4]], [[3zhg|3zhg]]</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=3zg5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zg5 OCA], [https://pdbe.org/3zg5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zg5 RCSB], [https://www.ebi.ac.uk/pdbsum/3zg5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zg5 ProSAT]</span></td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Serine-type_D-Ala-D-Ala_carboxypeptidase Serine-type D-Ala-D-Ala carboxypeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.16.4 3.4.16.4] </span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3zg5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zg5 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3zg5 RCSB], [http://www.ebi.ac.uk/pdbsum/3zg5 PDBsum]</span></td></tr>
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</table>
</table>
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<div style="background-color:#fffaf0;">
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== Function ==
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== Publication Abstract from PubMed ==
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[https://www.uniprot.org/uniprot/A0A0H3JPA5_STAAM A0A0H3JPA5_STAAM]
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The expression of penicillin binding protein 2a (PBP2a) is the basis for the broad clinical resistance to the beta-lactam antibiotics by methicillin-resistant Staphylococcus aureus (MRSA). The high-molecular mass penicillin binding proteins of bacteria catalyze in separate domains the transglycosylase and transpeptidase activities required for the biosynthesis of the peptidoglycan polymer that comprises the bacterial cell wall. In bacteria susceptible to beta-lactam antibiotics, the transpeptidase activity of their penicillin binding proteins (PBPs) is lost as a result of irreversible acylation of an active site serine by the beta-lactam antibiotics. In contrast, the PBP2a of MRSA is resistant to beta-lactam acylation and successfully catalyzes the DD-transpeptidation reaction necessary to complete the cell wall. The inability to contain MRSA infection with beta-lactam antibiotics is a continuing public health concern. We report herein the identification of an allosteric binding domain-a remarkable 60 A distant from the DD-transpeptidase active site-discovered by crystallographic analysis of a soluble construct of PBP2a. When this allosteric site is occupied, a multiresidue conformational change culminates in the opening of the active site to permit substrate entry. This same crystallographic analysis also reveals the identity of three allosteric ligands: muramic acid (a saccharide component of the peptidoglycan), the cell wall peptidoglycan, and ceftaroline, a recently approved anti-MRSA beta-lactam antibiotic. The ability of an anti-MRSA beta-lactam antibiotic to stimulate allosteric opening of the active site, thus predisposing PBP2a to inactivation by a second beta-lactam molecule, opens an unprecedented realm for beta-lactam antibiotic structure-based design.
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How allosteric control of Staphylococcus aureus penicillin binding protein 2a enables methicillin resistance and physiological function.,Otero LH, Rojas-Altuve A, Llarrull LI, Carrasco-Lopez C, Kumarasiri M, Lastochkin E, Fishovitz J, Dawley M, Hesek D, Lee M, Johnson JW, Fisher JF, Chang M, Mobashery S, Hermoso JA Proc Natl Acad Sci U S A. 2013 Oct 1. PMID:24085846<ref>PMID:24085846</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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==See Also==
==See Also==
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*[[Penicillin-binding protein|Penicillin-binding protein]]
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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__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Serine-type D-Ala-D-Ala carboxypeptidase]]
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[[Category: Large Structures]]
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[[Category: Staphylococcus aureus]]
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[[Category: Staphylococcus aureus subsp. aureus Mu50]]
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[[Category: Hermoso, J A]]
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[[Category: Synthetic construct]]
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[[Category: Otero, L H]]
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[[Category: Hermoso JA]]
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[[Category: Rojas-Altuve, A]]
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[[Category: Otero LH]]
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[[Category: Allosteric site]]
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[[Category: Rojas-Altuve A]]
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[[Category: B- lactam antibiotic]]
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[[Category: Hydrolase]]
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[[Category: Penicillin binding protein]]
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Current revision

Crystal structure of PBP2a from MRSA in complex with peptidoglycan analogue at allosteric

PDB ID 3zg5

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