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==Crystal Structure of Mevalonate-3-Kinase from Thermoplasma acidophilum (Mevalonate 3-Phosphate/ADP Bound)==
<StructureSection load='4rkz' size='340' side='right'caption='[[4rkz]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4rkz]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Thermoplasma_acidophilum_DSM_1728 Thermoplasma acidophilum DSM 1728]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RKZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RKZ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3S4:(3R)-5-HYDROXY-3-METHYL-3-(PHOSPHONOOXY)PENTANOIC+ACID'>3S4</scene>, <scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=4rkz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rkz OCA], [https://pdbe.org/4rkz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rkz RCSB], [https://www.ebi.ac.uk/pdbsum/4rkz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rkz ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MV3K_THEAC MV3K_THEAC] Phosphorylates mevalonate to form mevalonate 3-phosphate. Functions in an alternative Thermoplasma-type mevalonate pathway, which passes through mevalonate 3-phosphate rather than mevalonate 5-phosphate.<ref>PMID:24755225</ref> <ref>PMID:24914732</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
In animals, cholesterol is made from 5-carbon building blocks produced by the mevalonate pathway. Drugs that inhibit the mevalonate pathway such as atorvastatin (Lipitor) have led to successful treatments for high cholesterol in humans. Another potential target for the inhibition of cholesterol synthesis is mevalonate diphosphate decarboxylase (MDD), which catalyzes the phosphorylation of (R)-mevalonate diphosphate, followed by decarboxylation to yield isopentenyl pyrophosphate. We recently discovered an MDD homolog, mevalonate-3-kinase (M3K) from Thermoplasma acidophilum, which catalyzes the identical phosphorylation of (R)-mevalonate, but without concomitant decarboxylation. Thus, M3K catalyzes half the reaction of the decarboxylase, allowing us to separate features of the active site that are required for decarboxylation from features required for phosphorylation. Here we determine the crystal structure of M3K in the apo form, and with bound substrates, and compare it to MDD structures. Structural and mutagenic analysis reveals modifications that allow M3K to bind mevalonate rather than mevalonate diphosphate. Comparison to homologous MDD structures show that both enzymes employ analogous Arg or Lys residues to catalyze phosphate transfer. However, an invariant active site Asp/Lys pair of MDD previously thought to play a role in phosphorylation is missing in M3K with no functional replacement. Thus, we suggest that the invariant Asp/Lys pair in MDD may be critical for decarboxylation rather than phosphorylation. This article is protected by copyright. All rights reserved.

Structural Analysis of Mevalonate-3-Kinase Provides Insight Into The Mechanisms of Isoprenoid Pathway Decarboxylases.,Vinokur JM, Korman TP, Sawaya MR, Collazo M, Cascio D, Bowie JU Protein Sci. 2014 Nov 25. doi: 10.1002/pro.2607. PMID:25422158<ref>PMID:25422158</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4rkz" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Thermoplasma acidophilum DSM 1728]]
[[Category: Bowie JU]]
[[Category: Cascio D]]
[[Category: Sawaya MR]]
[[Category: Vinokur JM]]