1NW5

Structure of the beta class N6-adenine DNA methyltransferase RsrI bound to S-ADENOSYLMETHIONINE

Summary for 1NW5

• Entry DOI: 10.2210/pdb1nw5/pdb
• Related: 1EG2 1NW6 1NW7 1NW8
• Descriptor: MODIFICATION METHYLASE RSRI, CHLORIDE ION, S-ADENOSYLMETHIONINE, ... (4 entities in total)
• Functional Keywords: adenine dna methyltransferase, s-adenosylmethionine, rossmann fold, transferase
• Biological source: Rhodobacter sphaeroides
• Total number of polymer chains: 1
• Total formula weight: 36136.08

Authors

Thomas, C.B.,Scavetta, R.D.,Gumport, R.I.,Churchill, M.E.A. (deposition date: 2003-02-05, release date: 2003-07-29, Last modification date: 2024-02-14)

Primary citation

Thomas, C.B.,Scavetta, R.D.,Gumport, R.I.,Churchill, M.E.A.
Structures of liganded and unliganded RsrI N6-adenine DNA methyltransferase: a distinct orientation for active cofactor binding
J.Biol.Chem., 278:26094-26101, 2003

PubMed Abstract: 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.

PubMed: 12732637
DOI: 10.1074/jbc.M303751200

Experimental method

X-RAY DIFFRACTION (2.05 Å)