View source for 7xhw


==Crystal structure of metallo-beta-lactamase IMP-1==
<StructureSection load='7xhw' size='340' side='right'caption='[[7xhw]], [[Resolution|resolution]] 1.94&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7xhw]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7XHW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7XHW 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]] 1.94&#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=7xhw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7xhw OCA], [https://pdbe.org/7xhw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7xhw RCSB], [https://www.ebi.ac.uk/pdbsum/7xhw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7xhw ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/K0ITE2_ECOLX K0ITE2_ECOLX] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
IMP-type metallo-beta-lactamases confer resistance to carbapenems and a broad spectrum of beta-lactam antibiotics. IMP-6 and IMP-1 differ by only a point mutation: Ser262 in IMP-1 and Gly262 in IMP-6. The kcat/Km values of IMP-1 for imipenem and meropenem are nearly identical; however, for IMP-6, the kcat/Km for meropenem is 7-fold that for imipenem. In clinical practice, this may result in an ineffective therapeutic regimen and, consequently, in treatment failure. Here, we report the crystal structures of IMP-6 and IMP-1 with the same space group and similar cell constants at resolutions of 1.70 and 1.94 A, respectively. The overall structures of IMP-6 and IMP-1 are similar. However, the loop region (residues 60-66), which participates in substrate binding, is more flexible in IMP-6 than in IMP-1. This difference in flexibility determines the substrate specificity of IMP-type metallo-beta-lactamases for imipenem and meropenem. The amino acid at position 262 alters the mobility of His263; this affects the flexibility of the loop via a hydrogen bond with Pro68, which plays the role of a hinge in IMP-type metallo-beta-lactamases. The substitution of Pro68 with a glycine elicited an increase in the Km of IMP-6 for imipenem, whereas the affinity for meropenem remained unchanged.

Structural insights into the substrate specificity of IMP-6 and IMP-1 metallo-beta-lactamases.,Yamamoto K, Tanaka H, Kurisu G, Nakano R, Yano H, Sakai H J Biochem. 2022 Dec 27;173(1):21-30. doi: 10.1093/jb/mvac080. PMID:36174533<ref>PMID:36174533</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7xhw" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli]]
[[Category: Large Structures]]
[[Category: Kurisu G]]
[[Category: Nakano R]]
[[Category: Sakai H]]
[[Category: Tanaka H]]
[[Category: Yamamoto K]]
[[Category: Yano H]]