1xi2
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Quinone Reductase 2 in Complex with Cancer Prodrug CB1954
OverviewOverview
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.
About this StructureAbout this Structure
1XI2 is a Single protein structure of sequence from Homo sapiens with , and as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of quinone reductase 2 in complex with cancer prodrug CB1954., Fu Y, Buryanovskyy L, Zhang Z, Biochem Biophys Res Commun. 2005 Oct 14;336(1):332-8. PMID:16129418
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