1g64
From Proteopedia
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THE THREE-DIMENSIONAL STRUCTURE OF ATP:CORRINOID ADENOSYLTRANSFERASE FROM SALMONELLA TYPHIMURIUM. COBALAMIN/ATP TERNARY COMPLEX
Overview
In Salmonella typhimurium, formation of the cobalt-carbon bond in the, biosynthetic pathway for adenosylcobalamin is catalyzed by the product of, the cobA gene which encodes a protein of 196 amino acid residues. This, enzyme is an ATP:co(I)rrinoid adenosyltransferase which transfers an, adenosyl moiety from MgATP to a broad range of co(I)rrinoid substrates, that are believed to include cobinamide, its precursor cobyric acid and, probably others as yet unidentified, and hydroxocobalamin. Three X-ray, structures of CobA are reported here: its substrate-free form, a complex, of CobA with MgATP, and a ternary complex of CobA with MgATP and, hydroxycobalamin to 2.1, 1.8, and 2.1 A resolution, respectively. These, structures show that the enzyme is a homodimer. In the apo structure, the, polypeptide chain extends from Arg(28) to Lys(181) and consists of an, alpha/beta structure built from a six-stranded parallel beta-sheet with, strand order 324516. The topology of this fold is very similar to that, seen in RecA protein, helicase domain, F(1)ATPase, and adenosylcobinamide, kinase/adenosylcobinamide guanylyltransferase where a P-loop is located at, the end of the first strand. Strikingly, the nucleotide in the MgATP.CobA, complex binds to the P-loop of CobA in the opposite orientation compared, to all the other nucleotide hydrolases. That is, the gamma-phosphate binds, at the location normally occupied by the alpha-phosphate. The unusual, orientation of the nucleotide arises because this enzyme transfers an, adenosyl group rather than the gamma-phosphate. In the ternary complex, the binding site for hydroxycobalamin is located in a shallow bowl-shaped, depression at the C-terminal end of the beta-sheet of one subunit;, however, the active site is capped by the N-terminal helix from the, symmetry-related subunit that now extends from Gln(7) to Ala(24). The, lower ligand of cobalamin is well-ordered and interacts mostly with the, N-terminal helix of the symmetry-related subunit. Interestingly, there are, few interactions between the protein and the polar side chains of the, corrin ring which accounts for the broad specificity of this enzyme. The, corrin ring is oriented such that the cobalt atom is located approximately, 6.1 A from C5' of the ribose and is beyond the range of nucleophilic, attack. This suggests that a conformational change occurs in the ternary, complex when Co(III) is reduced to Co(I).
About this Structure
1G64 is a Single protein structure of sequence from Salmonella typhimurium with MG, B12 and ATP as ligands. Active as Cob(I)yrinic acid a,c-diamide adenosyltransferase, with EC number 2.5.1.17 Full crystallographic information is available from OCA.
Reference
Three-dimensional structure of ATP:corrinoid adenosyltransferase from Salmonella typhimurium in its free state, complexed with MgATP, or complexed with hydroxycobalamin and MgATP., Bauer CB, Fonseca MV, Holden HM, Thoden JB, Thompson TB, Escalante-Semerena JC, Rayment I, Biochemistry. 2001 Jan 16;40(2):361-74. PMID:11148030
Page seeded by OCA on Tue Nov 20 15:44:25 2007
