6d5k | pdb_00006d5k

Structure of Human ATP:Cobalamin Adenosyltransferase bound to ATP, and Adenosylcobalamin

spinqualitylabelsall models 6d5k, resolution 2.85Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6d5k is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.85Å Ligands: 5AD, ATP, B12, EPE, MG, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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. Function MMAB_HUMAN Publication Abstract from PubMed A sophisticated intracellular trafficking pathway in humans is used to tailor vitamin B12 into its active cofactor forms, and to deliver it to two known B12-dependent enzymes. Herein, we report an unexpected strategy for cellular retention of B12, an essential and reactive cofactor. If methylmalonyl-CoA mutase is unavailable to accept the coenzyme B12 product of adenosyltransferase, the latter catalyzes homolytic scission of the cobalt-carbon bond in an unconventional reversal of the nucleophilic displacement reaction that was used to make it. The resulting homolysis product binds more tightly to adenosyltransferase than does coenzyme B12, facilitating cofactor retention. We have trapped, and characterized spectroscopically, an intermediate in which the cobalt-carbon bond is weakened prior to being broken. The physiological relevance of this sacrificial catalytic activity for cofactor retention is supported by the significantly lower coenzyme B12 concentration in patients with dysfunctional methylmalonyl-CoA mutase but normal adenosyltransferase activity. Sacrificial Cobalt-Carbon Bond Homolysis in Coenzyme B12 as a Cofactor Conservation Strategy.,Campanello GC, Ruetz M, Dodge GJ, Gouda H, Gupta A, Twahir UT, Killian MM, Watkins D, Rosenblatt DS, Brunold TC, Warncke K, Smith JL, Banerjee R J Am Chem Soc. 2018 Oct 8. doi: 10.1021/jacs.8b08659. PMID:30282455 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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