PDBsum entry 1sip

Hydrolase(acid proteinase)

PDB id: 1sip

Contents

Protein chain

99 a.a.

Waters ×40

References listed in PDB file

Key reference

• Title: Alternative native flap conformation revealed by 2.3 a resolution structure of siv proteinase.
• Authors: A.F.Wilderspin, R.J.Sugrue.
• Ref.: J Mol Biol, 1994, 239, 97.
• PubMed id: 8196050

Abstract

A large conformational change is observed between HIV-1 proteinase in the ligand-free state and in complexes with transition-state inhibitors. Crystal structures of this enzyme have either the flaps open for the native or ligand-free enzyme or the flaps closed for peptidomimetic ligand-bound enzyme. We describe the structure of native recombinant SIV proteinase which like other retroviral proteinases crystallizes as a perfect 2-fold symmetric dimer but in a different crystal packing arrangement. In contrast to HIV-1 PR we show that SIV proteinase in the ligand-free state adopts the closed flaps conformation, demonstrating that ligand binding is not a prerequisite for the closed flaps conformation. The catalytic water was clearly observed between the two aspartates which were not perfectly co-planar, and in this structure the active site cleft is more restricted than for either inhibitor bound or ligand-free HIV-1 proteinase. Accommodation of two bulkier side-chains in the simian enzyme core has resulted in a more exposed N terminus than for HIV-1 PR which we predict could enhance autocatalytic cleavage at the N terminus.

Secondary reference #1

• Title: Purification of crystallizable recombinant sivmac251-32h proteinase.
• Authors: R.J.Sugrue, N.Almond, P.Kitchin, S.M.Richardson, A.F.Wilderspin.
• Ref.: Protein Expr Purif, 1994, 5, 76-83.
• PubMed id: 8167477

Secondary reference #2

• Title: Crystallization and preliminary X-Ray investigation of recombinant simian immunodeficiency virus proteinase.
• Authors: A.F.Wilderspin, R.J.Sugrue.
• Ref.: J Mol Biol, 1993, 231, 1139-1142.
• PubMed id: 8515473