1nw6
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Structure of the beta class N6-adenine DNA methyltransferase RsrI bound to sinefungin
OverviewOverview
The structures of RsrI DNA methyltransferase (M.RsrI) bound to the, substrate S-adenosyl-l-methionine (AdoMet), the product, S-adenosyl-l-homocysteine (AdoHcy), the inhibitor sinefungin, as well as a, mutant apo-enzyme have been determined by x-ray crystallography. Two, distinct binding configurations were observed for the three ligands. The, substrate AdoMet adopts a bent shape that directs the activated methyl, group toward the active site near the catalytic DPPY motif. The product, AdoHcy and the competitive inhibitor sinefungin bind with a straight, conformation in which the amino acid moiety occupies a position near the, activated methyl group in the AdoMet complex. Analysis of ligand binding, in comparison with other DNA methyltransferases reveals a small, common, subset of available conformations for the ligand. The structures of M.RsrI, with the non-substrate ligands contained a bound chloride ion in the, AdoMet carboxylate-binding pocket, explaining its inhibition by chloride, salts. The L72P mutant of M.RsrI is the first DNA methyltransferase, structure without bound ligand. With respect to the wild-type protein, it, had a larger ligand-binding pocket and displayed movement of a loop, (223-227) that is responsible for binding the ligand, which may account, for the weaker affinity of the L72P mutant for AdoMet. These studies show, the subtle changes in the tight specific interactions of substrate, product, and an inhibitor with M.RsrI and help explain how each displays, its unique effect on the activity of the enzyme.
About this StructureAbout this Structure
1NW6 is a Single protein structure of sequence from Rhodobacter sphaeroides with CL and SFG as ligands. Active as Site-specific DNA-methyltransferase (adenine-specific), with EC number 2.1.1.72 Full crystallographic information is available from OCA.
ReferenceReference
Structures of liganded and unliganded RsrI N6-adenine DNA methyltransferase: a distinct orientation for active cofactor binding., Thomas CB, Scavetta RD, Gumport RI, Churchill ME, J Biol Chem. 2003 Jul 11;278(28):26094-101. Epub 2003 May 4. PMID:12732637
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