1YTI

SIV PROTEASE CRYSTALLIZED WITH PEPTIDE PRODUCT

Summary for 1YTI

• Entry DOI: 10.2210/pdb1yti/pdb
• Descriptor: SIV PROTEASE, PEPTIDE PRODUCT (3 entities in total)
• Functional Keywords: complex (hydrolase-peptide, ) aids, polyprotein, hydrolase, aspartyl protease, endonuclease, rna-directed dna polymerase, complex (hydrolase-peptide) complex, complex (hydrolase/peptide)
• Biological source: Simian immunodeficiency virus
• Cellular location: Matrix protein p17: Virion (Potential). Capsid protein p24: Virion (Potential). Nucleocapsid protein p7: Virion (Potential). Reverse transcriptase/ribonuclease H: Virion (Potential). Integrase: Virion (Potential): P05896
• Total number of polymer chains: 2
• Total formula weight: 11305.07

Authors

Rose, R.B.,Craik, C.S.,Douglas, N.L.,Stroud, R.M. (deposition date: 1996-08-01, release date: 1997-03-12, Last modification date: 2024-02-14)

Primary citation

Rose, R.B.,Craik, C.S.,Douglas, N.L.,Stroud, R.M.
Three-dimensional structures of HIV-1 and SIV protease product complexes.
Biochemistry, 35:12933-12944, 1996

PubMed Abstract: Strain is eliminated as a factor in hydrolysis of the scissile peptide bond by human immunodeficiency virus (HIV)-1 and simian immunodeficiency virus (SIV), based on the first eight complexes of products of hydrolysis with the enzymes. The carboxyl group generated at the scissile bond interacts with both catalytic aspartic acids. The structures directly suggest the interactions of the gemdiol intermediate with the active site. Based on the structures, the nucleophilic water is displaced stereospecifically by substrate binding toward one catalytic aspartic acid, while the scissile carbonyl becomes hydrogen bonded to the other catalytic aspartic acid in position for hydrolysis. Crystal structures for two N-terminal (P) products and two C-terminal (Q) products provide unambiguous density for the ligands at 2.2-2.6 A resolution and 17-21% R factors. The N-terminal product, Ac-S-L-N-F/, overlaps closely with the N-terminal sequences of peptidomimetic inhibitors bound to the protease. Comparison of the two C-terminal products, /F-L-E-K and /F(NO2)-E-A-Nle-S, indicates that the P2' residue is highly constrained, while the positioning of the P1' and P3' residues are sequence dependent.

PubMed: 8841139
DOI: 10.1021/bi9612733

Experimental method

X-RAY DIFFRACTION (2.2 Å)