2r6t

Structure of a R132K variant PduO-type ATP:co(I)rrinoid adenosyltransferase from Lactobacillus reuteri complexed with ATP

spinqualitylabelsall models 2r6t, resolution 2.61Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2r6t is a 2 chain structure with sequence from Atcc 23272. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ATP, MG Related: 2r6x Gene: cobA (ATCC 23272) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum 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 ATP:Co(I)rrinoid adenosyltransferase (ACA) catalyzes the conversion of cobalamin to coenzyme B12, an essential cofactor in animal metabolism. Several mutations of conserved residues in the active site of human ACA have been identified in humans with methylmalonic aciduria. However, the catalytic role of these residues remains unclear. To better understand the function of these residues and to determine how the enzyme promotes catalysis, several variants of a human-type ACA from the lactic acid bacterium Lactobacillus reuteri (LrPduO) were kinetically and structurally characterized. Kinetic analyses of a series of alternate nucleotides were also performed. Substrate inhibition was observed at subsaturating concentrations of ATP, consistent with an ordered binding scheme where ATP is bound first by the enzyme. Modification or elimination of an active site, inter-subunit salt bridge resulted in a reduced "on" rate for ATP binding, with a less significant disruption in the rate of subsequent catalytic steps. Kinetic and structural data demonstrate that residue Arg132 is not involved in orienting ATP in the active site but, rather, it stabilizes the altered substrate in the transition state. Two functional groups of ATP explain the reduced ability of the enzyme to use alternate nucleotides: the amino group at the C-6 position of ATP contributes approximately 6 kcal/mol of free energy to ground state binding, and the nitrogen at the N-7 position assists in coordinating the magnesium ion in the active site. This study provides new insight into the role of substrate binding determinants and active site residues in the reaction catalyzed by a human-type ACA. Structural and functional analyses of the human-type corrinoid adenosyltransferase (PduO) from Lactobacillus reuteri.,Mera PE, St Maurice M, Rayment I, Escalante-Semerena JC Biochemistry. 2007 Dec 4;46(48):13829-36. Epub 2007 Nov 8. PMID:17988155 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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