View source for 5acs


==Y233A-Investigation of the impact from residues W228 and Y233 in the metallo-beta-lactamase GIM-1==
<StructureSection load='5acs' size='340' side='right'caption='[[5acs]], [[Resolution|resolution]] 1.46&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5acs]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ACS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ACS 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]] 1.459&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</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=5acs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5acs OCA], [https://pdbe.org/5acs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5acs RCSB], [https://www.ebi.ac.uk/pdbsum/5acs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5acs ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q704V1_PSEAI Q704V1_PSEAI] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Metallo-beta-lactamases (MBLs) hydrolyze virtually all beta-lactam antibiotics including penicillins, cephalosporins, and carbapenems. The worldwide emergence of antibiotic resistant bacteria harboring MBLs poses an increasing clinical threat. The MBL German IMipenemase-1 (GIM-1) possess a more narrow and hydrophobic active-site, compared to other MBLs. The GIM-1 active-site groove is shaped by the presence of the aromatic side chains of tryptophan at residue 228 and tyrosine at residue 233, positions where other MBLs harbor hydrophilic residues. To investigate the importance of these two residues eight site-directed mutants of GIM-1: W228R/A/Y/S and Y233N/A/I/S; were generated and characterized using enzyme kinetics, thermostability assays, and determination of minimum inhibitory concentration (MIC) for representative beta-lactams. Structures of selected mutants were obtained by X-ray crystallography and their interactions with beta-lactam substrates modelled in silico. Steady-state kinetics revealed both positions to be important to GIM-1 activity but that the effects of individual mutations varied depending on the beta-lactam substrate. Activity against type 1 substrates bearing electron-donating C3/C4 substituents (cefoxitin, meropenem) could be enhanced by mutations at position 228, whereas hydrolysis of type 2 substrates (benzylpenicillin, ampicillin, ceftazidime, imipenem) with methyl or positively charged substituents was favored by mutations at position 233. The crystal structures show that mutations at position 228, or the Y233A variant, alter the conformations of GIM-1 loop L1 rather than that of loop L3 on which the mutations are located. Taken together, these data show that point mutations at both positions 228 and 233 can influence the catalytic properties and the structure of GIM-1.

Investigating the role of residues W228 and Y233 in the structure and activity of the GIM-1 metallo-beta-lactamase.,Skagseth S, Carlsen TJ, Bjerga GE, Spencer J, Samuelsen O, Leiros HS Antimicrob Agents Chemother. 2015 Dec 7. pii: AAC.02017-15. PMID:26643332<ref>PMID:26643332</ref>

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

==See Also==
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Pseudomonas aeruginosa]]
[[Category: Bjerga GEK]]
[[Category: Carlsen TJ]]
[[Category: Leiros H-KS]]
[[Category: Samuelsen O]]
[[Category: Skagseth S]]
[[Category: Spencer J]]