|
|
| Line 1: |
Line 1: |
| | | | |
| | ==Structural insights of MAT enzymes: MATa2b complexed with SAM and PPNP== | | ==Structural insights of MAT enzymes: MATa2b complexed with SAM and PPNP== |
| - | <StructureSection load='4ndn' size='340' side='right' caption='[[4ndn]], [[Resolution|resolution]] 2.34Å' scene=''> | + | <StructureSection load='4ndn' size='340' side='right'caption='[[4ndn]], [[Resolution|resolution]] 2.34Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4ndn]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NDN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4NDN FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4ndn]] is a 6 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=4NDN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NDN FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PPK:(DIPHOSPHONO)AMINOPHOSPHONIC+ACID'>PPK</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PPK:(DIPHOSPHONO)AMINOPHOSPHONIC+ACID'>PPK</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ktt|4ktt]], [[4ktv|4ktv]]</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=4ndn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ndn OCA], [https://pdbe.org/4ndn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ndn RCSB], [https://www.ebi.ac.uk/pdbsum/4ndn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ndn ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MAT2A, AMS2, MATA2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), MAT2B, TGR, MSTP045, Nbla02999, UNQ2435/PRO4995 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Methionine_adenosyltransferase Methionine adenosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.6 2.5.1.6] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ndn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ndn OCA], [http://pdbe.org/4ndn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ndn RCSB], [http://www.ebi.ac.uk/pdbsum/4ndn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ndn ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/METK2_HUMAN METK2_HUMAN]] Catalyzes the formation of S-adenosylmethionine from methionine and ATP. [[http://www.uniprot.org/uniprot/MAT2B_HUMAN MAT2B_HUMAN]] Non-catalytic regulatory subunit of S-adenosylmethionine synthetase 2 (MAT2A), an enzyme that catalyzes the formation of S-adenosylmethionine from methionine and ATP. Regulates the activity of S-adenosylmethionine synthetase 2 by changing its kinetic properties, rendering the enzyme more susceptible to S-adenosylmethionine inhibition.<ref>PMID:10644686</ref> | + | [https://www.uniprot.org/uniprot/METK2_HUMAN METK2_HUMAN] Catalyzes the formation of S-adenosylmethionine from methionine and ATP. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 21: |
Line 18: |
| | </div> | | </div> |
| | <div class="pdbe-citations 4ndn" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4ndn" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[S-adenosylmethionine synthetase 3D structures|S-adenosylmethionine synthetase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Methionine adenosyltransferase]] | + | [[Category: Large Structures]] |
| - | [[Category: Antonyuk, S V]] | + | [[Category: Antonyuk SV]] |
| - | [[Category: Hasnain, S S]] | + | [[Category: Hasnain SS]] |
| - | [[Category: Lu, S C]] | + | [[Category: Lu SC]] |
| - | [[Category: Marina, A]] | + | [[Category: Marina A]] |
| - | [[Category: Mato, J M]] | + | [[Category: Mato JM]] |
| - | [[Category: Murray, B]] | + | [[Category: Murray B]] |
| - | [[Category: Rojas, A L]] | + | [[Category: Rojas AL]] |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
METK2_HUMAN Catalyzes the formation of S-adenosylmethionine from methionine and ATP.
Publication Abstract from PubMed
S-Adenosylmethionine (SAMe) is the principal methyl donor of the cell and is synthesized via an ATP-driven process by methionine adenosyltransferase (MAT) enzymes. It is tightly linked with cell proliferation in liver and colon cancer. In humans, there are three genes, mat1A, mat2A and mat2B, which encode MAT enzymes. mat2A and mat2B transcribe MATalpha2 and MATbeta enzyme subunits, respectively, with catalytic and regulatory roles. The MATalpha2beta complex is expressed in nearly all tissues and is thought to be essential in providing the necessary SAMe flux for methylation of DNA and various proteins including histones. In human hepatocellular carcinoma mat2A and mat2B genes are upregulated, highlighting the importance of the MATalpha2beta complex in liver disease. The individual subunits have been structurally characterized but the nature of the complex has remained elusive despite its existence having been postulated for more than 20 years and the observation that MATbeta is often co-localized with MATalpha2. Though SAMe can be produced by MAT(alpha2)4 alone, this paper shows that the V max of the MATalpha2beta complex is three- to fourfold higher depending on the variants of MATbeta that participate in complex formation. Using X-ray crystallography and solution X-ray scattering, the first structures are provided of this 258 kDa functional complex both in crystals and solution with an unexpected stoichiometry of 4alpha2 and 2betaV2 subunits. It is demonstrated that the N-terminal regulates the activity of the complex and it is shown that complex formation takes place surprisingly via the C-terminal of MATbetaV2 that buries itself in a tunnel created at the interface of the MAT(alpha2)2. The structural data suggest a unique mechanism of regulation and provide a gateway for structure-based drug design in anticancer therapies.
Structure and function study of the complex that synthesizes S-adenosylmethionine.,Murray B, Antonyuk SV, Marina A, Van Liempd SM, Lu SC, Mato JM, Hasnain SS, Rojas AL IUCrJ. 2014 Jun 12;1(Pt 4):240-9. doi: 10.1107/S2052252514012585. eCollection, 2014 Jul 1. PMID:25075345[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Murray B, Antonyuk SV, Marina A, Van Liempd SM, Lu SC, Mato JM, Hasnain SS, Rojas AL. Structure and function study of the complex that synthesizes S-adenosylmethionine. IUCrJ. 2014 Jun 12;1(Pt 4):240-9. doi: 10.1107/S2052252514012585. eCollection, 2014 Jul 1. PMID:25075345 doi:http://dx.doi.org/10.1107/S2052252514012585
|
