View source for 5gme


==Crystal structure of Sulfolobus solfataricus Diphosphomevalonate decarboxylase in complex with ADP==
<StructureSection load='5gme' size='340' side='right'caption='[[5gme]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5gme]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Sacs2 Sacs2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5GME OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5GME FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=DP6:(3R)-3-HYDROXY-5-{[(R)-HYDROXY(PHOSPHONOOXY)PHOSPHORYL]OXY}-3-METHYLPENTANOIC+ACID'>DP6</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5gmd|5gmd]]</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SSO2989 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=273057 SACS2])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Diphosphomevalonate_decarboxylase Diphosphomevalonate decarboxylase], with EC number [http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5gme FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5gme OCA], [http://pdbe.org/5gme PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5gme RCSB], [http://www.ebi.ac.uk/pdbsum/5gme PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5gme ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/DMD_SULSO DMD_SULSO]] Catalyzes the decarboxylation of mevalonate 5-diphosphate (MVAPP) to isopentenyl diphosphate (IPP). Functions in the mevalonate (MVA) pathway leading to IPP, a key precursor for the biosynthesis of isoprenoid compounds such as archaeal membrane lipids.<ref>PMID:23378249</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The biosynthesis of isopentenyl diphosphate, a fundamental precursor for isoprenoids, via the mevalonate pathway is completed by diphosphomevalonate decarboxylase. This enzyme catalyzes the formation of isopentenyl diphosphate through the ATP-dependent phosphorylation of the 3-hydroxyl group of (R)-5-diphosphomevalonate followed by decarboxylation coupled with the elimination of the 3-phosphate group. In this reaction, a conserved aspartate residue has been proposed to be involved in the phosphorylation step as the general base catalyst that abstracts a proton from the 3-hydroxyl group. In this study, the catalytic mechanism of this rare type of decarboxylase is re-investigated by structural and mutagenic studies on the enzyme from a thermoacidophilic archaeon Sulfolobus solfataricus The crystal structures of the archaeal enzyme in complex with (R)-5-diphosphomevalonate and adenosine 5'-O-(3-thio)triphosphate or with (R)-5-diphosphomevalonate and ADP are newly solved, and theoretical analysis based on the structure suggests the inability of proton abstraction by the conserved aspartate residue, Asp-281. Site-directed mutagenesis on Asp-281 creates mutants that only show diphosphomevalonate 3-kinase activity, demonstrating that the residue is required in the process of phosphate elimination/decarboxylation, rather than in the preceding phosphorylation step. These results enable discussion of the catalytic roles of the aspartate residue and provide clear proof of the involvement of a long predicted intermediate, (R)-3-phospho-5-diphosphomevalonate, in the reaction of the enzyme.

A Single Amino Acid Mutation Converts (R)-5-Diphosphomevalonate Decarboxylase into a Kinase.,Motoyama K, Unno H, Hattori A, Takaoka T, Ishikita H, Kawaide H, Yoshimura T, Hemmi H J Biol Chem. 2017 Feb 10;292(6):2457-2469. doi: 10.1074/jbc.M116.752535. Epub, 2016 Dec 21. PMID:28003359<ref>PMID:28003359</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5gme" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Diphosphomevalonate decarboxylase]]
[[Category: Large Structures]]
[[Category: Sacs2]]
[[Category: Hattori, A]]
[[Category: Hemmi, H]]
[[Category: Unno, H]]
[[Category: Adp]]
[[Category: Lyase]]
[[Category: Sulfolobus solfataricus]]