1SIP

ALTERNATIVE NATIVE FLAP CONFORMATION REVEALED BY 2.3 ANGSTROMS RESOLUTION STRUCTURE OF SIV PROTEINASE

Summary for 1SIP

• Entry DOI: 10.2210/pdb1sip/pdb
• Descriptor: UNLIGANDED SIV PROTEASE (2 entities in total)
• Functional Keywords: hydrolase(acid proteinase)
• Biological source: Simian immunodeficiency virus
• Total number of polymer chains: 1
• Total formula weight: 10787.41

Authors

Wilderspin, A.F. (deposition date: 1994-04-13, release date: 1994-08-31, Last modification date: 2024-02-14)

Primary citation

Wilderspin, A.F.,Sugrue, R.J.
Alternative native flap conformation revealed by 2.3 A resolution structure of SIV proteinase.
J.Mol.Biol., 239:97-103, 1994

PubMed 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.

PubMed: 8196050
DOI: 10.1006/jmbi.1994.1353

Experimental method

X-RAY DIFFRACTION (2.3 Å)