3PAX

THE CATALYTIC FRAGMENT OF POLY(ADP-RIBOSE) POLYMERASE COMPLEXED WITH 3-METHOXYBENZAMIDE

Summary for 3PAX

• Entry DOI: 10.2210/pdb3pax/pdb
• Descriptor: POLY(ADP-RIBOSE) POLYMERASE, 3-METHOXYBENZAMIDE (3 entities in total)
• Functional Keywords: transferase, glycosyltransferase, nad(+) adp-ribosyltransferase
• Biological source: Gallus gallus (chicken)
• Cellular location: Nucleus: P26446
• Total number of polymer chains: 1
• Total formula weight: 40566.51

Authors

Ruf, A.,Schulz, G.E. (deposition date: 1997-11-25, release date: 1998-05-27, Last modification date: 2024-05-22)

Primary citation

Ruf, A.,de Murcia, G.,Schulz, G.E.
Inhibitor and NAD+ binding to poly(ADP-ribose) polymerase as derived from crystal structures and homology modeling.
Biochemistry, 37:3893-3900, 1998

PubMed Abstract: 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.

PubMed: 9521710
DOI: 10.1021/bi972383s

Experimental method

X-RAY DIFFRACTION (2.4 Å)