View source for 5ksh


==Crystal structure of penicillin-binding protein 2 from Neisseria gonorrhoeae containing an A501T mutation associated with cephalosporin resistance==
<StructureSection load='5ksh' size='340' side='right'caption='[[5ksh]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5ksh]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Neisseria_gonorrhoeae Neisseria gonorrhoeae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KSH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5KSH FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5ksh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ksh OCA], [https://pdbe.org/5ksh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ksh RCSB], [https://www.ebi.ac.uk/pdbsum/5ksh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ksh ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PBP2_NEIGO PBP2_NEIGO] Synthesis of cross-linked peptidoglycan from the lipid intermediates.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Resistance of Neisseria gonorrhoeae to expanded-spectrum cephalosporins such as ceftriaxone and cefixime has increased markedly in the past decade. The primary cephalosporin resistance determinant is a mutated penA gene, which encodes the essential peptidoglycan transpeptidase, penicillin-binding protein 2 (PBP2). Decreased susceptibility and resistance can be conferred by mosaic penA alleles containing upward of 60 amino acid changes relative to wild-type PBP2, or by nonmosaic alleles with relatively few mutations, the most important of which occurs at Ala501 located near the active site of PBP2. Recently, fully cefixime- and ceftriaxone-resistant clinical isolates that harbored a mosaic penA allele with an A501P mutation were identified. To examine the potential of mutations at Ala501 to increase resistance to expanded-spectrum cephalosporins, we randomized codon 501 in a mosaic penA allele and transformed N. gonorrhoeae to increased cefixime resistance. Interestingly, only five substitutions of Ala501 (A501V, A501T, A501P, A501R, and A501S) that increased resistance and preserved essential transpeptidase function were isolated. To understand their structural implications, these mutations were introduced into the nonmosaic PBP2-6140CT, which contains four C-terminal mutations present in PBP2 from the penicillin-resistant strain FA6140. The crystal structure of PBP2-6140CT-A501T was determined and revealed ordering of a loop near the active site and a new hydrogen bond involving Thr501 that connects the loop and the SxxK conserved active site motif. The structure suggests that increased rigidity in the active site region is a mechanism for cephalosporin resistance mediated by Ala501 mutations in PBP2.

Alanine 501 Mutations in Penicillin-Binding Protein 2 from Neisseria gonorrhoeae: Structure, Mechanism, and Effects on Cephalosporin Resistance and Biological Fitness.,Tomberg J, Fedarovich A, Vincent LR, Jerse AE, Unemo M, Davies C, Nicholas RA Biochemistry. 2017 Feb 28;56(8):1140-1150. doi: 10.1021/acs.biochem.6b01030. Epub, 2017 Feb 16. PMID:28145684<ref>PMID:28145684</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5ksh" style="background-color:#fffaf0;"></div>

==See Also==
*[[Penicillin-binding protein 3D structures|Penicillin-binding protein 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Neisseria gonorrhoeae]]
[[Category: Davies C]]
[[Category: Fedarovich A]]