PDBsum entry 1q9s

Transferase

PDB id: 1q9s

Contents

Protein chain

149 a.a. *

Ligands

ADP

FMN

Metals

_MG

Waters ×86

* Residue conservation analysis

PDB id:

1q9s

Name:

Transferase

Title:

Crystal structure of riboflavin kinase with ternary product complex

Structure:

Hypothetical protein flj11149. Chain: a. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: flj11149. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.

Resolution:

2.42Å R-factor: 0.199 R-free: 0.260

Authors:

S.Karthikeyan,Q.Zhou,A.L.Osterman,H.Zhang

Key ref:

S.Karthikeyan et al. (2003). Ligand binding-induced conformational changes in riboflavin kinase: structural basis for the ordered mechanism. Biochemistry, 42, 12532-12538. PubMed id: 14580199 DOI: 10.1021/bi035450t

Date:

25-Aug-03 Release date: 16-Dec-03

Protein chain

Q969G6  (RIFK_HUMAN) -  Riboflavin kinase from Homo sapiens

Seq: 155 a.a.

Struc: 149 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.2.7.1.26 - riboflavin kinase.
• Reaction: riboflavin + ATP = FMN + ADP + H⁺

riboflavin + ATP = FMN (Bound ligand (Het Group name = FMN) corresponds exactly) + ADP (Bound ligand (Het Group name = ADP) corresponds exactly) + H(+)

• Cofactor: Mg(2+) or Zn(2+) or Mn(2+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1021/bi035450t

Biochemistry 42:12532-12538 (2003)

PubMed id: 14580199

Ligand binding-induced conformational changes in riboflavin kinase: structural basis for the ordered mechanism.

S.Karthikeyan, Q.Zhou, A.L.Osterman, H.Zhang.

ABSTRACT

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.