1q9s

From Proteopedia

Revision as of 14:43, 15 February 2008

Crystal structure of riboflavin kinase with ternary product complex

Overview

Riboflavin kinase (RFK) is an essential enzyme catalyzing the, phosphorylation of riboflavin (vitamin B(2)) in the presence of ATP and, Mg(2+) to form the active cofactor FMN, which can be further converted to, FAD. Previously, the crystal structures of RFKs from human and, Schizosaccharomyces pombe have been determined in the apo form and in, complex with MgADP. These structures revealed that RFK adopts a novel, kinase fold and utilizes a unique nucleotide binding site. The structures, of the flavin-bound RFK obtained by soaking pre-existing crystals were, also reported. Because of crystal packing restraints, these flavin-bound, RFK complexes adopt conformations nearly identical with that of, corresponding flavin-free structures. Here we report the structure of, human RFK cocrystallized with both MgADP and FMN. Drastic conformational, changes associated with flavin binding are observed primarily at the, so-called Flap I and Flap II loop regions. As a result, the bound FMN, molecule now interacts with the enzyme extensively and is well-ordered., Residues from Flap II interact with Flap I and shield the FMN molecule, from the solvent. The conformational changes in Flap I resulted in a new, Mg(2+) coordination pattern in which a FMN phosphate oxygen and Asn36 side, chain carbonyl are directly coordinating to the Mg(2+) ion. The proposed, catalytic base Glu86 is well-positioned for activation of the O5' hydroxyl, group of riboflavin for the phosphoryl transfer reaction. The structural, data obtained so far on human and yeast RFK complexes provide a rationale, for the ordered kinetic mechanism of RFK.

About this Structure

1Q9S is a Single protein structure of sequence from Homo sapiens with , and as ligands. Active as Riboflavin kinase, with EC number 2.7.1.26 Full crystallographic information is available from OCA.

Reference

Ligand binding-induced conformational changes in riboflavin kinase: structural basis for the ordered mechanism., Karthikeyan S, Zhou Q, Osterman AL, Zhang H, Biochemistry. 2003 Nov 4;42(43):12532-8. PMID:14580199

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