3FIV

CRYSTAL STRUCTURE OF FELINE IMMUNODEFICIENCY VIRUS PROTEASE COMPLEXED WITH A SUBSTRATE

Summary for 3FIV

• Entry DOI: 10.2210/pdb3fiv/pdb
• Related: 2FIV
• Related PRD ID: PRD_000243
• Descriptor: FELINE IMMUNODEFICIENCY VIRUS PROTEASE, ACE-ALN-VAL-LEU-ALA-GLU-ALN-NH2, SULFATE ION, ... (4 entities in total)
• Functional Keywords: aspartic protease, retroviral protease, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Feline immunodeficiency virus
• Total number of polymer chains: 4
• Total formula weight: 28450.73

Authors

Schalk-Hihi, C.,Lubkowski, J.,Zdanov, A.,Wlodawer, A.,Gustchina, A. (deposition date: 1997-07-09, release date: 1997-11-12, Last modification date: 2023-08-09)

Primary citation

Laco, G.S.,Schalk-Hihi, C.,Lubkowski, J.,Morris, G.,Zdanov, A.,Olson, A.,Elder, J.H.,Wlodawer, A.,Gustchina, A.
Crystal structures of the inactive D30N mutant of feline immunodeficiency virus protease complexed with a substrate and an inhibitor.
Biochemistry, 36:10696-10708, 1997

PubMed Abstract: Crystal structures of complexes of a D30N mutant of feline immunodeficiency virus protease (FIV PR) complexed with a statine-based inhibitor (LP-149), as well as with a substrate based on a modification of this inhibitor (LP-149S), have been solved and refined at resolutions of 2.0 and 1.85 A, respectively. Both the inhibitor and the substrate are bound in the active site of the mutant protease in a similar mode, which also resembles the mode of binding of LP-149 to the native protease. The carbonyl oxygen of the scissile bond in the substrate is not hydrated and is located within the distance of a hydrogen bond to an amido nitrogen atom from one of the two asparagines in the active site of the enzyme. The nitrogen atom of the scissile bond is 3.25 A from the conserved water molecule (Wat301). A model of a tetrahedral intermediate bound to the active site of the native enzyme was built by considering the interactions observed in all three crystal structures of FIV PR. Molecular dynamics simulations of this model bound to native wild-type FIV PR were carried out, to investigate the final stages of the catalytic mechanism of aspartic proteases.

PubMed: 9271500
DOI: 10.1021/bi9707436

Experimental method

X-RAY DIFFRACTION (1.85 Å)