2r42

<StructureSection load='2r42' size='340' side='right' caption='[[2r42]], [[Resolution|resolution]] 2.40&Aring;' scene=''>

<table><tr><td colspan='2'>[[2r42]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2R42 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2R42 FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FPS:S-[(2E,6E)-3,7,11-TRIMETHYLDODECA-2,6,10-TRIENYL]+TRIHYDROGEN+THIODIPHOSPHATE'>FPS</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>

<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2r3v|2r3v]]</td></tr>

<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Mvk ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus])</td></tr>

<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mevalonate_kinase Mevalonate kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.36 2.7.1.36] </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=2r42 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2r42 OCA], [http://pdbe.org/2r42 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2r42 RCSB], [http://www.ebi.ac.uk/pdbsum/2r42 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2r42 ProSAT]</span></td></tr>

[[http://www.uniprot.org/uniprot/KIME_RAT KIME_RAT]] Note=Mutation in the mevalonate kinase gene causes mevalonicaciduria.

[[http://www.uniprot.org/uniprot/KIME_RAT KIME_RAT]] May be a regulatory site in cholesterol biosynthetic pathway.

<div style="background-color:#fffaf0;">

== Publication Abstract from PubMed ==

Mevalonate kinase (MK), which catalyzes a key reaction in polyisoprenoid and sterol metabolism in many organisms, is subject to feedback regulation by farnesyl diphosphate and related compounds. The structures of human mevalonate kinase and a binary complex of the rat enzyme incubated with farnesyl thiodiphosphate (FSPP) are reported. Significant FSPP hydrolysis occurs under crystallization conditions; this results in detection of farnesyl thiophosphate (FSP) in the structure of the binary complex. Farnesyl thiodiphosphate competes with substrate ATP to produce feedback inhibition of mevalonate kinase. The binding sites for these metabolites overlap, with the phosphate of FSP nearly superimposed on ATP's beta-phosphate and FSP's polyisoprenoid chain overlapping ATP's adenosine moiety. Several hydrophobic amino acid side chains are positioned near the polyisoprenoid chain of FSP and their functional significance has been evaluated in mutagenesis experiments with human MK, which exhibits the highest reported sensitivity to feedback inhibition. Results suggest that single and double mutations at T104 and I196 produce a significant inflation of the K(i) for FSPP (approximately 40-fold for T104A/I196A). Such an effect persists when K(i) values are normalized for effects on the K(m) for ATP, suggesting that it may be possible to engineer MK proteins with altered sensitivity to feedback inhibition. Comparison of animal MK protein alignments and structures with those of a MK protein from Streptococcus pneumoniae indicates that sequence differences between N- and C-terminal domains correlate with differences in interdomain angles. Bacterial MK proteins exhibit more solvent exposure of feedback inhibitor binding sites and, consequently, weaker binding of these inhibitors.

 

<div class="pdbe-citations 2r42" style="background-color:#fffaf0;"></div>

== References ==

[[Category: Mevalonate kinase]]

[[Category: Fu, Z]]

[[Category: Kim, J P]]

[[Category: Miziorko, H M]]

[[Category: Voynova, N E]]

[[Category: Transferase]]