View source for 5har


==OXA-163 beta-lactamase - S70G mutant==
<StructureSection load='5har' size='340' side='right'caption='[[5har]], [[Resolution|resolution]] 1.74&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5har]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Enterobacter_cloacae Enterobacter cloacae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HAR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5HAR 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]] 1.74&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</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=5har FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5har OCA], [https://pdbe.org/5har PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5har RCSB], [https://www.ebi.ac.uk/pdbsum/5har PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5har ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/F6KZJ2_ENTCL F6KZJ2_ENTCL] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Serine beta-lactamases are bacterial enzymes that hydrolyze beta-lactam antibiotics. They utilize an active-site serine residue as a nucleophile, forming an acyl-enzyme intermediate during hydrolysis. In this study, thermal denaturation experiments as well as X-ray crystallography were performed to test the effect of substitution of the catalytic serine with glycine on protein stability in serine beta-lactamases. Six different enzymes comprising representatives from each of the three classes of serine beta-lactamases were examined, including TEM-1, CTX-M-14, and KPC-2 of class A, P99 of class C, and OXA-48 and OXA-163 of class D. For each enzyme, the wild type and a serine-to-glycine mutant were evaluated for stability. The glycine mutants all exhibited enhanced thermostability compared to that of the wild type. In contrast, alanine substitutions of the catalytic serine in TEM-1, OXA-48, and OXA-163 did not alter stability, suggesting removal of the Cbeta atom is key to the stability increase associated with the glycine mutants. The X-ray crystal structures of P99 S64G, OXA-48 S70G and S70A, and OXA-163 S70G suggest that removal of the side chain of the catalytic serine releases steric strain to improve enzyme stability. Additionally, analysis of the torsion angles at the nucleophile position indicates that the glycine mutants exhibit improved distance and angular parameters of the intrahelical hydrogen bond network compared to those of the wild-type enzymes, which is also consistent with increased stability. The increased stability of the mutants indicates that the enzyme pays a price in stability for the presence of a side chain at the catalytic serine position but that the cost is necessary in that removal of the serine drastically impairs function. These findings support the stability-function hypothesis, which states that active-site residues are optimized for substrate binding and catalysis but that the requirements for catalysis are often not consistent with the requirements for optimal stability.

Removal of the Side Chain at the Active-Site Serine by a Glycine Substitution Increases the Stability of a Wide Range of Serine beta-Lactamases by Relieving Steric Strain.,Stojanoski V, Adamski CJ, Hu L, Mehta SC, Sankaran B, Zwart P, Prasad BV, Palzkill T Biochemistry. 2016 May 3;55(17):2479-90. doi: 10.1021/acs.biochem.6b00056. Epub, 2016 Apr 22. PMID:27073009<ref>PMID:27073009</ref>

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

==See Also==
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Enterobacter cloacae]]
[[Category: Large Structures]]
[[Category: Adamski CJ]]
[[Category: Hu L]]
[[Category: Mehta SC]]
[[Category: Palzkill TG]]
[[Category: Prasad BVV]]
[[Category: Sankaran B]]
[[Category: Stojanoski V]]