2pax
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THE CATALYTIC FRAGMENT OF POLY(ADP-RIBOSE) POLYMERASE COMPLEXED WITH 4-AMINO-1,8-NAPHTHALIMIDE
OverviewOverview
Inhibitors of poly(ADP-ribose) polymerase (PARP, EC 2.4.2.30) are of, clinical interest because they have potential for improving radiation, therapy and chemotherapy of cancer. The refined binding structures of four, such inhibitors are reported together with the refined structure of the, unligated catalytic fragment of the enzyme. Following their design, all, inhibitors bind at the position of the nicotinamide moiety of the, substrate NAD+. The observed binding mode suggests inhibitor improvements, that avoid other NAD(+)-binding enzymes. Because the binding pocket of, NAD+ has been strongly conserved during evolution, the homology with, ADP-ribosylating bacterial toxins could be used to extend the bound, nicotinamide, which is marked by the inhibitors, to the full NAD+, molecule.
About this StructureAbout this Structure
2PAX is a Single protein structure of sequence from Gallus gallus with 4AN as ligand. Active as NAD(+) ADP-ribosyltransferase, with EC number 2.4.2.30 Full crystallographic information is available from OCA.
ReferenceReference
Inhibitor and NAD+ binding to poly(ADP-ribose) polymerase as derived from crystal structures and homology modeling., Ruf A, de Murcia G, Schulz GE, Biochemistry. 1998 Mar 17;37(11):3893-900. PMID:9521710
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