1kvk | pdb_00001kvk

The Structure of Binary complex between a Mammalian Mevalonate Kinase and ATP: Insights into the Reaction Mechanism and Human Inherited Disease

spinqualitylabelsall models 1kvk, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1kvk is a 1 chain structure with sequence from Buffalo rat. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ATP, MG Activity: Mevalonate kinase, with EC number 2.7.1.36 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease [KIME_RAT] Note=Mutation in the mevalonate kinase gene causes mevalonicaciduria. Function [KIME_RAT] May be a regulatory site in cholesterol biosynthetic pathway. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Mevalonate kinase catalyzes the ATP-dependent phosphorylation of mevalonic acid to form mevalonate 5-phosphate, a key intermediate in the pathways of isoprenoids and sterols. Deficiency in mevalonate kinase activity has been linked to mevalonic aciduria and hyperimmunoglobulinemia D/periodic fever syndrome (HIDS). The crystal structure of rat mevalonate kinase in complex with MgATP has been determined at 2.4-A resolution. Each monomer of this dimeric protein is composed of two domains with its active site located at the domain interface. The enzyme-bound ATP adopts an anti conformation, in contrast to the syn conformation reported for Methanococcus jannaschii homoserine kinase. The Mg(2+) ion is coordinated to both beta- and gamma-phosphates of ATP and side chains of Glu(193) and Ser(146). Asp(204) is making a salt bridge with Lys(13), which in turn interacts with the gamma-phosphate. A model of mevalonic acid can be placed near the gamma-phosphoryl group of ATP; thus, the C5 hydroxyl is located within 4 A from Asp(204), Lys(13), and the gamma-phosphoryl of ATP. This arrangement of residues strongly suggests: 1) Asp(204) abstracts the proton from C5 hydroxyl of mevalonate; 2) the penta-coordinated gamma-phosphoryl group may be stabilized by Mg(2+), Lys(13), and Glu(193); and 3) Lys(13) is likely to influence the pK(a) of the C5 hydroxyl of the substrate. V377I and I268T are the most common mutations found in patients with HIDS. Val(377) is located over 18 A away from the active site and a conservative replacement with Ile is unlikely to yield an inactive or unstable protein. Ile-268 is located at the dimer interface, and its Thr substitution may disrupt dimer formation. The structure of a binary complex between a mammalian mevalonate kinase and ATP: insights into the reaction mechanism and human inherited disease.,Fu Z, Wang M, Potter D, Miziorko HM, Kim JJ J Biol Chem. 2002 May 17;277(20):18134-42. Epub 2002 Feb 27. PMID:11877411 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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