View source for 7rxx


==Human Methionine Adenosyltransferase 2A bound to Methylthioadenosine and two sulfate in the active site==
<StructureSection load='7rxx' size='340' side='right'caption='[[7rxx]], [[Resolution|resolution]] 1.25&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7rxx]] is a 1 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=7RXX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RXX 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]] 1.25&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ALA:ALANINE'>ALA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MTA:5-DEOXY-5-METHYLTHIOADENOSINE'>MTA</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=P3G:3,6,9,12,15-PENTAOXAHEPTADECANE'>P3G</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=7rxx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rxx OCA], [https://pdbe.org/7rxx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rxx RCSB], [https://www.ebi.ac.uk/pdbsum/7rxx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rxx 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 ==
Human methionine adenosyltransferase MAT2A provides S-adenosyl-l-methionine (AdoMet) for methyl-transfer reactions. Epigenetic methylations influence expression patterns in development and in cancer. Transition-state analysis and kinetic studies have described the mechanism of AdoMet and triphosphate formation at the catalytic site. Hydrolysis of triphosphate to pyrophosphate and phosphate by MAT2A is required for product release and proceeds through a second chemical transition state. Crystal structures of MAT2A with analogues of AdoMet and pyrophosphate were obtained in the presence of Mg(2+), Al(3+), and F(-). MgF3(-) is trapped as a PO3(-) mimic in a structure with malonate filling the pyrophosphate site. NMR demonstrates that MgF3(-) and AlF3(0) are bound by MAT2A as mimics of the departing phosphoryl group. Crystallographic analysis reveals a planar MgF3(-) acting to mimic a phosphoryl (PO3(-)) leaving group. The modeled transition state with PO3(-) has the phosphorus atom sandwiched symmetrically and equidistant (approximately 2 A) between a pyrophosphate oxygen and the water nucleophile. A catalytic site arginine directs the nucleophilic water to the phosphoryl leaving group. The catalytic geometry of the transition-state reconstruction predicts a loose transition state with characteristics of symmetric nucleophilic displacement.

Mechanism of Triphosphate Hydrolysis by Human MAT2A at 1.07 A Resolution.,Ghosh A, Niland CN, Cahill SM, Karadkhelkar NM, Schramm VL J Am Chem Soc. 2021 Oct 20. doi: 10.1021/jacs.1c09328. PMID:34668717<ref>PMID:34668717</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7rxx" 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: Fedorov E]]
[[Category: Ghosh A]]
[[Category: Niland CN]]
[[Category: Schramm VL]]