PDBsum entry 2qx9

Oxidoreductase

PDB id: 2qx9

Contents

Protein chain

230 a.a. *

Ligands

FAD ×2

ML2 ×2

Metals

_ZN ×2

Waters ×145

* Residue conservation analysis

PDB id:

2qx9

Name:

Oxidoreductase

Title:

Crystal structure of quinone reductase ii

Structure:

Ribosyldihydronicotinamide dehydrogenase [quinone]. Chain: a, b. Synonym: nrh dehydrogenase [quinone] 2, quinone reductase 2, qr2, nrh:quinone oxidoreductase 2. Engineered: yes

Source:

Homo sapiens. Human. Gene: nqo2, nmor2. Expressed in: escherichia coli.

Resolution:

2.31Å R-factor: 0.213 R-free: 0.286

Authors:

B.Calamini,B.D.Santarsiero,J.A.Boutin,A.D.Mesecar

Key ref:

B.Calamini et al. (2008). Kinetic, thermodynamic and X-ray structural insights into the interaction of melatonin and analogues with quinone reductase 2. Biochem J, 413, 81-91. PubMed id: 18254726

Date:

10-Aug-07 Release date: 02-Sep-08

Protein chains

P16083  (NQO2_HUMAN) -  Ribosyldihydronicotinamide dehydrogenase [quinone] from Homo sapiens

Seq: 231 a.a.

Struc: 230 a.a.*

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

Enzyme reactions

• Enzyme class: E.C.1.10.5.1 - ribosyldihydronicotinamide dehydrogenase (quinone).
• Reaction: 1-(beta-D-ribofuranosyl)-1,4-dihydronicotinamide + a quinone + H⁺ = beta-nicotinamide D-riboside + a quinol

1-(beta-D-ribofuranosyl)-1,4-dihydronicotinamide (Bound ligand (Het Group name = ML2) matches with 44.00% similarity) + quinone + H(+) = beta-nicotinamide D-riboside + quinol

• Cofactor: FAD; Zn(2+)

FAD (Bound ligand (Het Group name = FAD) corresponds exactly) Zn(2+)

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

reference

Biochem J 413:81-91 (2008)

PubMed id: 18254726

Kinetic, thermodynamic and X-ray structural insights into the interaction of melatonin and analogues with quinone reductase 2.

B.Calamini, B.D.Santarsiero, J.A.Boutin, A.D.Mesecar.

ABSTRACT

Melatonin exerts its biological effects through at least two transmembrane G-protein-coupled receptors, MT1 and MT2, and a lower-affinity cytosolic binding site, designated MT3. MT3 has recently been identified as QR2 (quinone reductase 2) (EC 1.10.99.2) which is of significance since it links the antioxidant effects of melatonin to a mechanism of action. Initially, QR2 was believed to function analogously to QR1 in protecting cells from highly reactive quinones. However, recent studies indicate that QR2 may actually transform certain quinone substrates into more highly reactive compounds capable of causing cellular damage. Therefore it is hypothesized that inhibition of QR2 in certain cases may lead to protection of cells against these highly reactive species. Since melatonin is known to inhibit QR2 activity, but its binding site and mode of inhibition are not known, we determined the mechanism of inhibition of QR2 by melatonin and a series of melatonin and 5-hydroxytryptamine (serotonin) analogues, and we determined the X-ray structures of melatonin and 2-iodomelatonin in complex with QR2 to between 1.5 and 1.8 A (1 A=0.1 nm) resolution. Finally, the thermodynamic binding constants for melatonin and 2-iodomelatonin were determined by ITC (isothermal titration calorimetry). The kinetic results indicate that melatonin is a competitive inhibitor against N-methyldihydronicotinamide (K(i)=7.2 microM) and uncompetitive against menadione (K(i)=92 microM), and the X-ray structures shows that melatonin binds in multiple orientations within the active sites of the QR2 dimer as opposed to an allosteric site. These results provide new insights into the binding mechanisms of melatonin and analogues to QR2.