1kz8

From Proteopedia

Revision as of 11:39, 21 February 2008

CRYSTAL STRUCTURE OF PORCINE FRUCTOSE-1,6-BISPHOSPHATASE COMPLEXED WITH A NOVEL ALLOSTERIC-SITE INHIBITOR

Overview

The synthesis and in vitro structure-activity relationships (SAR) of a novel series of anilinoquinazolines as allosteric inhibitors of fructose-1,6-bisphosphatase (F16Bpase) are reported. The compounds have a different SAR as inhibitors of F16Bpase than anilinoquinazolines previously reported. Selective inhibition of F16Bpase can be attained through the addition of appropriate polar functional groups at the quinazoline 2-position, thus separating the F16Bpase inhibitory activity from the epidermal growth factor receptor tyrosine kinase inhibitory activity previously observed with similar structures. The compounds have been found to bind at a symmetry-repeated novel allosteric site at the subunit interface of the enzyme. Inhibition is brought about by binding to a loop comprised of residues 52-72, preventing the necessary participation of these residues in the assembly of the catalytic site. Mutagenesis studies have identified the key amino acid residues in the loop that are required for inhibitor recognition and binding.

About this Structure

1KZ8 is a Single protein structure of sequence from Sus scrofa with , , and as ligands. Active as Fructose-bisphosphatase, with EC number 3.1.3.11 Full crystallographic information is available from OCA.

Reference

Anilinoquinazoline inhibitors of fructose 1,6-bisphosphatase bind at a novel allosteric site: synthesis, in vitro characterization, and X-ray crystallography., Wright SW, Carlo AA, Carty MD, Danley DE, Hageman DL, Karam GA, Levy CB, Mansour MN, Mathiowetz AM, McClure LD, Nestor NB, McPherson RK, Pandit J, Pustilnik LR, Schulte GK, Soeller WC, Treadway JL, Wang IK, Bauer PH, J Med Chem. 2002 Aug 29;45(18):3865-77. PMID:12190310

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