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| | ==Structural model for Fe-containing human acireductone dioxygenase== | | ==Structural model for Fe-containing human acireductone dioxygenase== |
| - | <StructureSection load='7jxg' size='340' side='right'caption='[[7jxg]], [[NMR_Ensembles_of_Models | 6 NMR models]]' scene=''> | + | <StructureSection load='7jxg' size='340' side='right'caption='[[7jxg]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[7jxg]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7JXG OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7JXG FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7jxg]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7JXG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7JXG FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ADI1, MTCBP1, HMFT1638 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Acireductone_dioxygenase_(Fe(2+)-requiring) Acireductone dioxygenase (Fe(2+)-requiring)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.13.11.54 1.13.11.54] </span></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=7jxg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7jxg OCA], [https://pdbe.org/7jxg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7jxg RCSB], [https://www.ebi.ac.uk/pdbsum/7jxg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7jxg ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=7jxg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7jxg OCA], [http://pdbe.org/7jxg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7jxg RCSB], [http://www.ebi.ac.uk/pdbsum/7jxg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7jxg ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MTND_HUMAN MTND_HUMAN]] Catalyzes the formation of formate and 2-keto-4-methylthiobutyrate (KMTB) from 1,2-dihydroxy-3-keto-5-methylthiopentene (DHK-MTPene). Also down-regulates cell migration mediated by MMP14. Necessary for hepatitis C virus replication in an otherwise non-permissive cell line.[HAMAP-Rule:MF_03154]<ref>PMID:11602742</ref> <ref>PMID:15938715</ref> | + | [https://www.uniprot.org/uniprot/MTND_HUMAN MTND_HUMAN] Catalyzes the formation of formate and 2-keto-4-methylthiobutyrate (KMTB) from 1,2-dihydroxy-3-keto-5-methylthiopentene (DHK-MTPene). Also down-regulates cell migration mediated by MMP14. Necessary for hepatitis C virus replication in an otherwise non-permissive cell line.[HAMAP-Rule:MF_03154]<ref>PMID:11602742</ref> <ref>PMID:15938715</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | The metalloenzyme acireductone dioxygenase (ARD) shows metal-dependent physical and enzymatic activities depending upon the metal bound in the active site. The Fe(II)-bound enzyme catalyzes the penultimate step of the methionine salvage pathway, converting 1,2-dihydroxy-5-(methylthio)pent-1-en-3-one (acireductone) into formate and the ketoacid precursor of methionine, 2-keto-4-thiomethyl-2-oxobutanoate, using O2 as the oxidant. If Ni(II) is bound, an off-pathway shunt occurs, producing 3-methylthiopropionate, formate, and carbon monoxide from the same acireductone substrate. The solution structure of the Fe(II)-bound human enzyme, HsARD, is described and compared with the structures of Ni-bound forms of the closely related mouse enzyme, MmARD. Potential rationales for the different reactivities of the two isoforms are discussed. The human enzyme has been found to regulate the activity of matrix metalloproteinase I (MMP-I), which is involved in tumor metastasis, by binding the cytoplasmic transmembrane tail peptide of MMP-I. Nuclear magnetic resonance titration of HsARD with the MMP-I tail peptide permits identification of the peptide binding site on HsARD, a cleft anterior to the metal binding site adjacent to a dynamic proline-rich loop.
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| - | A Model for the Solution Structure of Human Fe(II)-Bound Acireductone Dioxygenase and Interactions with the Regulatory Domain of Matrix Metalloproteinase I (MMP-I).,Liu X, Garber A, Ryan J, Deshpande A, Ringe D, Pochapsky TC Biochemistry. 2020 Nov 10;59(44):4238-4249. doi: 10.1021/acs.biochem.0c00724., Epub 2020 Nov 2. PMID:33135413<ref>PMID:33135413</ref>
| + | ==See Also== |
| - | | + | *[[Dioxygenase 3D structures|Dioxygenase 3D structures]] |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
| + | |
| - | <div class="pdbe-citations 7jxg" style="background-color:#fffaf0;"></div>
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| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Deshpande, A]] | + | [[Category: Deshpande A]] |
| - | [[Category: Garber, A]] | + | [[Category: Garber A]] |
| - | [[Category: Liu, X]] | + | [[Category: Liu X]] |
| - | [[Category: Pochapsky, T C]] | + | [[Category: Pochapsky TC]] |
| - | [[Category: Ringe, D]] | + | [[Category: Ringe D]] |
| - | [[Category: Ryan, J]] | + | [[Category: Ryan J]] |
| - | [[Category: Cancer]]
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| - | [[Category: Cupin barrel]]
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| - | [[Category: Methionine salvage]]
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| - | [[Category: Oxidoreductase]]
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