1yth
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Strain is eliminated as a factor in hydrolysis of the scissile peptide | + | 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. |
==About this Structure== | ==About this Structure== | ||
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[[Category: HIV-1 retropepsin]] | [[Category: HIV-1 retropepsin]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Craik, C | + | [[Category: Craik, C S.]] |
| - | [[Category: Douglas, N | + | [[Category: Douglas, N L.]] |
| - | [[Category: Rose, R | + | [[Category: Rose, R B.]] |
| - | [[Category: Stroud, R | + | [[Category: Stroud, R M.]] |
[[Category: ACE]] | [[Category: ACE]] | ||
[[Category: ) aids]] | [[Category: ) aids]] | ||
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[[Category: rna-directed dna polymerase]] | [[Category: rna-directed dna polymerase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:08:54 2008'' |
Revision as of 14:09, 21 February 2008
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SIV PROTEASE CRYSTALLIZED WITH PEPTIDE PRODUCT
Overview
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.
About this Structure
1YTH is a Single protein structure of sequence from Escherichia coli with as ligand. Active as HIV-1 retropepsin, with EC number 3.4.23.16 Full crystallographic information is available from OCA.
Reference
Three-dimensional structures of HIV-1 and SIV protease product complexes., Rose RB, Craik CS, Douglas NL, Stroud RM, Biochemistry. 1996 Oct 1;35(39):12933-44. PMID:8841139
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