View source for 3wwj


==Crystal structure of an engineered sitagliptin-producing transaminase, ATA-117-Rd11==
<StructureSection load='3wwj' size='340' side='right'caption='[[3wwj]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3wwj]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Arthrobacter_sp._KNK168 Arthrobacter sp. KNK168]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WWJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3WWJ 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]] 2.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</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=3wwj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wwj OCA], [https://pdbe.org/3wwj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3wwj RCSB], [https://www.ebi.ac.uk/pdbsum/3wwj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3wwj ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/F7J696_9MICC F7J696_9MICC] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
(R)-stereospecific amine transaminases (R-ATAs) are important biocatalysts for the production of (R)-amine compounds in a strict stereospecific manner. An improved R-ATA, ATA-117-Rd11, was successfully engineered for the manufacture of sitagliptin, a widely used therapeutic agent for type-2 diabetes. The effects of the individual mutations, however, have not yet been demonstrated due to the lack of experimentally determined structural information. Here we describe three crystal structures of the first isolated R-ATA, its G136F mutant and engineered ATA-117-Rd11, which indicated that the mutation introduced into the 136(th) residue altered the conformation of a loop next to the active site, resulting in a substrate-binding site with drastically modified volume, shape, and surface properties, to accommodate the large pro-sitagliptin ketone. Our findings provide a detailed explanation of the previously reported molecular engineering of ATA-117-Rd11 and propose that the loop near the active site is a new target for the rational design to change the substrate specificity of ATAs.

A new target region for changing the substrate specificity of amine transaminases.,Guan LJ, Ohtsuka J, Okai M, Miyakawa T, Mase T, Zhi Y, Hou F, Ito N, Iwasaki A, Yasohara Y, Tanokura M Sci Rep. 2015 Jun 1;5:10753. doi: 10.1038/srep10753. PMID:26030619<ref>PMID:26030619</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3wwj" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Arthrobacter sp. KNK168]]
[[Category: Large Structures]]
[[Category: Guan LJ]]
[[Category: Hou F]]
[[Category: Ito N]]
[[Category: Mase T]]
[[Category: Miyakawa T]]
[[Category: Ohtsuka J]]
[[Category: Okai M]]
[[Category: Tanokura M]]
[[Category: Yasohara Y]]
[[Category: Zhi Y]]