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| | <StructureSection load='4m3p' size='340' side='right'caption='[[4m3p]], [[Resolution|resolution]] 1.90Å' scene=''> | | <StructureSection load='4m3p' size='340' side='right'caption='[[4m3p]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4m3p]] is a 4 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=4M3P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4M3P FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4m3p]] 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=4M3P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4M3P FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HCS:2-AMINO-4-MERCAPTO-BUTYRIC+ACID'>HCS</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=SRT:S,R+MESO-TARTARIC+ACID'>SRT</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HCS:2-AMINO-4-MERCAPTO-BUTYRIC+ACID'>HCS</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=SRT:S,R+MESO-TARTARIC+ACID'>SRT</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1lt7|1lt7]], [[1lt8|1lt8]]</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=4m3p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m3p OCA], [https://pdbe.org/4m3p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4m3p RCSB], [https://www.ebi.ac.uk/pdbsum/4m3p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4m3p ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BHMT ([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/Betaine--homocysteine_S-methyltransferase Betaine--homocysteine S-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.5 2.1.1.5] </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=4m3p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m3p OCA], [http://pdbe.org/4m3p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4m3p RCSB], [http://www.ebi.ac.uk/pdbsum/4m3p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4m3p ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/BHMT1_HUMAN BHMT1_HUMAN]] Involved in the regulation of homocysteine metabolism. Converts betaine and homocysteine to dimethylglycine and methionine, respectively. This reaction is also required for the irreversible oxidation of choline. | + | [https://www.uniprot.org/uniprot/BHMT1_HUMAN BHMT1_HUMAN] Involved in the regulation of homocysteine metabolism. Converts betaine and homocysteine to dimethylglycine and methionine, respectively. This reaction is also required for the irreversible oxidation of choline. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Betaine--homocysteine S-methyltransferase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Diamond, C E]] | + | [[Category: Diamond CE]] |
| - | [[Category: Garrow, T A]] | + | [[Category: Garrow TA]] |
| - | [[Category: Jiracek, J]] | + | [[Category: Jiracek J]] |
| - | [[Category: Jungwirth, P]] | + | [[Category: Jungwirth P]] |
| - | [[Category: Koutmos, M]] | + | [[Category: Koutmos M]] |
| - | [[Category: Mladkova, J]] | + | [[Category: Mladkova J]] |
| - | [[Category: Paterova, J]] | + | [[Category: Paterova J]] |
| - | [[Category: Tryon, K]] | + | [[Category: Tryon K]] |
| - | [[Category: Yamada, K]] | + | [[Category: Yamada K]] |
| - | [[Category: Betaine]]
| + | |
| - | [[Category: Betaine-homocysteine s-methyltransferase activity]]
| + | |
| - | [[Category: Homocysteine]]
| + | |
| - | [[Category: Homocysteine s-methyltransferase activity]]
| + | |
| - | [[Category: Metal ion binding]]
| + | |
| - | [[Category: Methyltransferase activity]]
| + | |
| - | [[Category: Protein complex binding]]
| + | |
| - | [[Category: Tim beta/alpha-barrel]]
| + | |
| - | [[Category: Transferase]]
| + | |
| - | [[Category: Transferase activity]]
| + | |
| Structural highlights
Function
BHMT1_HUMAN Involved in the regulation of homocysteine metabolism. Converts betaine and homocysteine to dimethylglycine and methionine, respectively. This reaction is also required for the irreversible oxidation of choline.
Publication Abstract from PubMed
Betaine-homocysteine S-methyltransferase (BHMT) is a zinc-dependent methyltransferase that uses betaine as the methyl donor for the remethylation of homocysteine to form methionine. This reaction supports S-adenosylmethionine biosynthesis, which is required for hundreds of methylation reactions in humans. Herein we report that BHMT is activated by potassium ions with an apparent KM for K+ of about 100 microM. The presence of potassium ions lowers the apparent KM of the enzyme for homocysteine, but it does not affect the apparent KM for betaine or the apparent kcat for either substrate. We employed molecular dynamics (MD) simulations to theoretically predict and protein crystallography to experimentally localize the binding site(s) for potassium ion(s). Simulations predicted that K+ ion would interact with residues Asp26 and/or Glu159. Our crystal structure of BHMT bound to homocysteine confirms these sites of interaction and reveals further contacts between K+ ion and BHMT residues Gly27, Gln72, Gln247, and Gly298. The potassium binding residues in BHMT partially overlap with the previously identified DGG (Asp26-Gly27-Gly28) fingerprint in the Pfam 02574 group of methyltransferases. Subsequent biochemical characterization of several site-specific BHMT mutants confirmed the results obtained by the MD simulations and crystallographic data. Together, the data herein indicate that the role of potassium ions in BHMT is structural and that potassium ion facilitates the specific binding of homocysteine to the active site of the enzyme. Proteins 2014. (c) 2014 Wiley Periodicals, Inc.
Specific potassium ion interactions facilitate homocysteine binding to betaine-homocysteine S-methyltransferase.,Mladkova J, Hladilkova J, Diamond CE, Tryon K, Yamada K, Garrow TA, Jungwirth P, Koutmos M, Jiracek J Proteins. 2014 Jun 4. doi: 10.1002/prot.24619. PMID:24895213[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Mladkova J, Hladilkova J, Diamond CE, Tryon K, Yamada K, Garrow TA, Jungwirth P, Koutmos M, Jiracek J. Specific potassium ion interactions facilitate homocysteine binding to betaine-homocysteine S-methyltransferase. Proteins. 2014 Jun 4. doi: 10.1002/prot.24619. PMID:24895213 doi:http://dx.doi.org/10.1002/prot.24619
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