View source for 5ugh


==Crystal structure of Mat2a bound to the allosteric inhibitor PF-02929366==
<StructureSection load='5ugh' size='340' side='right'caption='[[5ugh]], [[Resolution|resolution]] 2.06&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5ugh]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UGH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5UGH 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]] 2.062&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8AJ:(E)-2-(7-CHLORO-5-PHENYL[1,2,4]TRIAZOLO[4,3-A]QUINOLIN-1-YL)-N,N-DIMETHYLETHEN-1-AMINE'>8AJ</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=5ugh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ugh OCA], [https://pdbe.org/5ugh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ugh RCSB], [https://www.ebi.ac.uk/pdbsum/5ugh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ugh ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/METK2_HUMAN METK2_HUMAN] Catalyzes the formation of S-adenosylmethionine from methionine and ATP.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
S-Adenosyl-L-methionine (SAM) is an enzyme cofactor used in methyl transfer reactions and polyamine biosynthesis. The biosynthesis of SAM from ATP and L-methionine is performed by the methionine adenosyltransferase enzyme family (Mat; EC 2.5.1.6). Human methionine adenosyltransferase 2A (Mat2A), the extrahepatic isoform, is often deregulated in cancer. We identified a Mat2A inhibitor, PF-9366, that binds an allosteric site on Mat2A that overlaps with the binding site for the Mat2A regulator, Mat2B. Studies exploiting PF-9366 suggested a general mode of Mat2A allosteric regulation. Allosteric binding of PF-9366 or Mat2B altered the Mat2A active site, resulting in increased substrate affinity and decreased enzyme turnover. These data support a model whereby Mat2B functions as an inhibitor of Mat2A activity when methionine or SAM levels are high, yet functions as an activator of Mat2A when methionine or SAM levels are low. The ramification of Mat2A activity modulation in cancer cells is also described.

Targeting S-adenosylmethionine biosynthesis with a novel allosteric inhibitor of Mat2A.,Quinlan CL, Kaiser SE, Bolanos B, Nowlin D, Grantner R, Karlicek-Bryant S, Feng JL, Jenkinson S, Freeman-Cook K, Dann SG, Wang X, Wells PA, Fantin VR, Stewart AE, Grant SK Nat Chem Biol. 2017 Jul;13(7):785-792. doi: 10.1038/nchembio.2384. Epub 2017 May , 29. PMID:28553945<ref>PMID:28553945</ref>

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

==See Also==
*[[S-adenosylmethionine synthetase 3D structures|S-adenosylmethionine synthetase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Feng J]]
[[Category: Kaiser SE]]
[[Category: Stewart AE]]