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| | <StructureSection load='3d4j' size='340' side='right'caption='[[3d4j]], [[Resolution|resolution]] 2.40Å' scene=''> | | <StructureSection load='3d4j' size='340' side='right'caption='[[3d4j]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3d4j]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3D4J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3D4J FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3d4j]] is a 2 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=3D4J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3D4J FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1fi4|1fi4]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MVD, MPD ([https://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'>[https://en.wikipedia.org/wiki/Diphosphomevalonate_decarboxylase Diphosphomevalonate decarboxylase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.1.33 4.1.1.33] </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=3d4j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3d4j OCA], [https://pdbe.org/3d4j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3d4j RCSB], [https://www.ebi.ac.uk/pdbsum/3d4j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3d4j ProSAT]</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=3d4j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3d4j OCA], [https://pdbe.org/3d4j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3d4j RCSB], [https://www.ebi.ac.uk/pdbsum/3d4j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3d4j ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/MVD1_HUMAN MVD1_HUMAN]] Performs the first committed step in the biosynthesis of isoprenes.
| + | [https://www.uniprot.org/uniprot/MVD1_HUMAN MVD1_HUMAN] Performs the first committed step in the biosynthesis of isoprenes. |
| | <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: Diphosphomevalonate decarboxylase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Battaile, K]] | + | [[Category: Battaile K]] |
| - | [[Category: Fu, Z]] | + | [[Category: Fu Z]] |
| - | [[Category: Herdendorf, T J]] | + | [[Category: Herdendorf TJ]] |
| - | [[Category: Kim, J J.P]] | + | [[Category: Kim J-JP]] |
| - | [[Category: Miziorko, H M]] | + | [[Category: Miziorko HM]] |
| - | [[Category: Voynova, N E]] | + | [[Category: Voynova NE]] |
| - | [[Category: Carboxylation]]
| + | |
| - | [[Category: Cholesterol biosynthesis]]
| + | |
| - | [[Category: Isopentenyl diphosphate]]
| + | |
| - | [[Category: Lipid synthesis]]
| + | |
| - | [[Category: Lyase]]
| + | |
| - | [[Category: Mevalonate diphosphate decarboxylase]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Steroid biosynthesis]]
| + | |
| - | [[Category: Sterol biosynthesis]]
| + | |
| Structural highlights
Function
MVD1_HUMAN Performs the first committed step in the biosynthesis of isoprenes.
Publication Abstract from PubMed
Expression in Escherichia coli of his-tagged human mevalonate diphosphate decarboxylase (hMDD) has expedited enzyme isolation, characterization, functional investigation of the mevalonate diphosphate binding site, and crystal structure determination (2.4A resolution). hMDD exhibits V(max)=6.1+/-0.5 U/mg; K(m) for ATP is 0.69+/-0.07 mM and K(m) for (R,S) mevalonate diphosphate is 28.9+/-3.3 microM. Conserved polar residues predicted to be in the hMDD active site were mutated to test functional importance. R161Q exhibits a approximately 1000-fold diminution in specific activity, while binding the fluorescent substrate analog, TNP-ATP, comparably to wild-type enzyme. Diphosphoglycolyl proline (K(i)=2.3+/-0.3 uM) and 6-fluoromevalonate 5-diphosphate (K(i)=62+/-5 nM) are competitive inhibitors with respect to mevalonate diphosphate. N17A exhibits a V(max)=0.25+/-0.0 2U/mg and a 15-fold inflation in K(m) for mevalonate diphosphate. N17A's K(i) values for diphosphoglycolyl proline and fluoromevalonate diphosphate are inflated (>70-fold and 40-fold, respectively) in comparison with wild-type enzyme. hMDD structure indicates the proximity (2.8A) between R161 and N17, which are located in an interior pocket of the active site cleft. The data suggest the functional importance of R161 and N17 in the binding and orientation of mevalonate diphosphate.
Human mevalonate diphosphate decarboxylase: characterization, investigation of the mevalonate diphosphate binding site, and crystal structure.,Voynova NE, Fu Z, Battaile KP, Herdendorf TJ, Kim JJ, Miziorko HM Arch Biochem Biophys. 2008 Dec 1;480(1):58-67. Epub 2008 Sep 18. PMID:18823933[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Voynova NE, Fu Z, Battaile KP, Herdendorf TJ, Kim JJ, Miziorko HM. Human mevalonate diphosphate decarboxylase: characterization, investigation of the mevalonate diphosphate binding site, and crystal structure. Arch Biochem Biophys. 2008 Dec 1;480(1):58-67. Epub 2008 Sep 18. PMID:18823933 doi:S0003-9861(08)00414-1
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