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==Human Ornithine Aminotransferase (hOAT) soaked with 5-aminovaleric acid==
<StructureSection load='7ta0' size='340' side='right'caption='[[7ta0]], [[Resolution|resolution]] 2.33&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7TA0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TA0 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]] 2.33&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=I3B:5-[({3-hydroxy-2-methyl-5-[(phosphonooxy)methyl]pyridin-4-yl}methyl)amino]pentanoic+acid'>I3B</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=7ta0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ta0 OCA], [https://pdbe.org/7ta0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ta0 RCSB], [https://www.ebi.ac.uk/pdbsum/7ta0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ta0 ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver and occurs predominantly in patients with underlying chronic liver diseases. Over the past decade, human ornithine aminotransferase (hOAT), which is an enzyme that catalyzes the metabolic conversion of ornithine into an intermediate for proline or glutamate synthesis, has been found to be overexpressed in HCC cells. hOAT has since emerged as a promising target for novel anticancer therapies, especially for the ongoing rational design effort to discover mechanism-based inactivators (MBIs). Despite the significance of hOAT in human metabolism and its clinical potential as a drug target against HCC, there are significant knowledge deficits with regard to its catalytic mechanism and structural characteristics. Ongoing MBI design efforts require in-depth knowledge of the enzyme active site, in particular, pKa values of potential nucleophiles and residues necessary for the molecular recognition of ligands. Here, we conducted a study detailing the fundamental active site properties of hOAT using stopped-flow spectrophotometry and X-ray crystallography. Our results quantitatively revealed the pH-dependence of the multi-step reaction mechanism and illuminated the roles of ornithine alpha- and delta-amino groups in substrate recognition and in facilitating catalytic turnover. These findings provided insights of the catalytic mechanism that could benefit the rational design of MBIs against hOAT. In addition, hOAT's substrate recognition and turnover of several fragment-sized alternative substrates, which could serve as structural templates for MBI design, were also elucidated.

Determination of the pH-Dependence, Substrate Specificity and Turnovers of Alternative Substrates for Human Ornithine Aminotransferase.,Butrin A, Butrin A, Wawrzak Z, Moran G, Liu D J Biol Chem. 2022 Apr 20:101969. doi: 10.1016/j.jbc.2022.101969. PMID:35460691<ref>PMID:35460691</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 7ta0" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Butrin A]]
[[Category: Liu D]]