2idx | pdb_00002idx

Structure of Human ATP:Cobalamin adenosyltransferase bound to ATP.

spinqualitylabelsall models 2idx, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2idx is a 3 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ATP, CL, MG, SO4 Gene: MMAB (HUMAN) Activity: Cob(I)yrinic acid a,c-diamide adenosyltransferase, with EC number 2.5.1.17 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum Disease [MMAB_HUMAN] Defects in MMAB are the cause of methylmalonic aciduria type cblB (MMAB) [MIM:251110]; also known as methylmalonic aciduria type B or vitamin B12-responsive methylmalonicaciduria of cblB complementation type. MMAB is a disorder of methylmalonate and cobalamin metabolism due to defective synthesis of adenosylcobalamin. Inheritance is autosomal recessive. 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 Mutations in the gene encoding human ATP:cobalamin adenosyltransferase (hATR) can result in the metabolic disorder known as methylmalonic aciduria (MMA). This enzyme catalyzes the final step in the conversion of cyanocobalamin (vitamin B12) to the essential human cofactor adenosylcobalamin. Here we present the 2.5 A crystal structure of ATP bound to hATR refined to an Rfree value of 25.2%. The enzyme forms a tightly associated trimer, where the monomer comprises a five-helix bundle and the active sites lie on the subunit interfaces. Only two of the three active sites within the trimer contain the bound ATP substrate, thereby providing examples of apo- and substrate-bound-active sites within the same crystal structure. Comparison of the empty and occupied sites indicates that twenty residues at the enzyme's N-terminus become ordered upon binding of ATP to form a novel ATP-binding site and an extended cleft that likely binds cobalamin. The structure explains the role of 20 invariant residues; six are involved in ATP binding, including Arg190, which hydrogen bonds to ATP atoms on both sides of the scissile bond. Ten of the hydrogen bonds are required for structural stability, and four are in positions to interact with cobalamin. The structure also reveals how the point mutations that cause MMA are deficient in these functions. Structure of ATP-bound human ATP:cobalamin adenosyltransferase.,Schubert HL, Hill CP Biochemistry. 2006 Dec 26;45(51):15188-96. PMID:17176040 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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