PDBsum entry 1xi2

Oxidoreductase

PDB id

1xi2

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Contents

			Protein chain

					230 a.a. *

			Ligands

					FAD ×2


					CB1 ×2

			Metals

					_ZN ×3

			Waters ×362

* Residue conservation analysis

PDB id:

1xi2

Links

Name:

Oxidoreductase

Title:

Quinone reductase 2 in complex with cancer prodrug cb1954

Structure:

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

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: nqo2, nmor2. Expressed in: escherichia coli. Expression_system_taxid: 562

Biol. unit:

Dimer (from PQS)

Resolution:

1.50Å

R-factor:

0.216

R-free:

0.233

Authors:

Y.Fu,L.Buryanovskyy,Z.Zhang

Key ref:

Y.Fu et al. (2005). Crystal structure of quinone reductase 2 in complex with cancer prodrug CB1954. Biochem Biophys Res Commun, 336, 332-338. PubMed id: 16129418 DOI: 10.1016/j.bbrc.2005.08.081

Date:

21-Sep-04

Release date:

30-Aug-05

PROCHECK

	Headers

	References

Protein chains

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

Seq: Struc:					231 a.a. 230 a.a.*

Key:

PfamA domain

Secondary structure

CATH domain

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



		Enzyme reactions

Enzyme class:

E.C.1.10.5.1 - ribosyldihydronicotinamide dehydrogenase (quinone).

[IntEnz] [ExPASy] [KEGG] [BRENDA]

Reaction:

1-(beta-D-ribofuranosyl)-1,4-dihydronicotinamide + a quinone + H⁺ = beta-nicotinamide D-riboside + a quinol

1-(beta-D-ribofuranosyl)-1,4-dihydronicotinamide	+	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

DOI no: 10.1016/j.bbrc.2005.08.081	Biochem Biophys Res Commun 336:332-338 (2005)
PubMed id: 16129418

Crystal structure of quinone reductase 2 in complex with cancer prodrug CB1954.
Y.Fu, L.Buryanovskyy, Z.Zhang.

ABSTRACT

CB1954 is a cancer pro-drug that can be activated through reduction by Escherichia coli nitro-reductases and quinone reductases. Human quinone reductase 2 is very efficient in the activation of CB1954, approximately 3000 times more efficient than human QR1 in terms of k(cat)/K(m). We have solved the three-dimensional structure of QR2 in complex with CB1954 to a nominal resolution of 1.5A. The complex structure indicates the essentiality of the two nitro groups: one nitro group forms hydrogen bonds with the side-chain of Asn161 of QR2 to hold the other nitro group in position for the reduction. We further conclude that residue 161, an Asn in QR2 and a His in QR1, is critical in differentiating the substrate specificities of these two enzymes. Mutation of Asn161 to His161 in QR2 resulted in the total loss of the enzymatic activity towards activation of CB1954, whereas the rates of reduction towards menadione are not altered.

Literature references that cite this PDB file's key reference

PubMed id

Reference

19265439

A.Maiti, P.V.Reddy, M.Sturdy, L.Marler, S.D.Pegan, A.D.Mesecar, J.M.Pezzuto, and M.Cushman (2009).
Synthesis of casimiroin and optimization of its quinone reductase 2 and aromatase inhibitory activities.

J Med Chem, 52, 1873-1884.

PDB codes:

3g5m 3gam

19236722

J.A.Winger, O.Hantschel, G.Superti-Furga, and J.Kuriyan (2009).
The structure of the leukemia drug imatinib bound to human quinone reductase 2 (NQO2).

BMC Struct Biol, 9, 7.

PDB code:

3fw1

18579530

Y.Fu, L.Buryanovskyy, and Z.Zhang (2008).
Quinone reductase 2 is a catechol quinone reductase.

J Biol Chem, 283, 23829-23835.

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.