1yti › Citations

Three-dimensional structures of HIV-1 and SIV protease product complexes.

Rose RB, Craik CS, Douglas NL, Stroud RM
Biochemistry 35 12933-44 (1996)
Related entries: 1ytg, 1yth, 1ytj

Cited: 21 times
EuropePMC logo PMID: 8841139

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.

Articles - 1yti mentioned but not cited (3)

  1. Dimer Interface Organization is a Main Determinant of Intermonomeric Interactions and Correlates with Evolutionary Relationships of Retroviral and Retroviral-Like Ddi1 and Ddi2 Proteases. Mótyán JA, Miczi M, Tőzsér J. Int J Mol Sci 21 E1352 (2020)
  2. Discovery of Novel µ-Opioid Receptor Inverse Agonist from a Combinatorial Library of Tetrapeptides through Structure-Based Virtual Screening. Poli G, Dimmito MP, Mollica A, Zengin G, Benyhe S, Zador F, Stefanucci A. Molecules 24 E3872 (2019)
  3. Evolution of drug resistance drives destabilization of flap region dynamics in HIV-1 protease. Rajendran M, Ferran MC, Mouli L, Babbitt GA, Lynch ML. Biophys Rep (N Y) 3 100121 (2023)


Articles citing this publication (18)

  1. How does a symmetric dimer recognize an asymmetric substrate? A substrate complex of HIV-1 protease. Prabu-Jeyabalan M, Nalivaika E, Schiffer CA. J Mol Biol 301 1207-1220 (2000)
  2. Drug resistance in HIV-1 protease: Flexibility-assisted mechanism of compensatory mutations. Piana S, Carloni P, Rothlisberger U. Protein Sci 11 2393-2402 (2002)
  3. Structural milestones in the reaction pathway of an amide hydrolase: substrate, acyl, and product complexes of cephalothin with AmpC beta-lactamase. Beadle BM, Trehan I, Focia PJ, Shoichet BK. Structure 10 413-424 (2002)
  4. A solution NMR study of the binding kinetics and the internal dynamics of an HIV-1 protease-substrate complex. Katoh E, Louis JM, Yamazaki T, Gronenborn AM, Torchia DA, Ishima R. Protein Sci 12 1376-1385 (2003)
  5. Viability of a drug-resistant human immunodeficiency virus type 1 protease variant: structural insights for better antiviral therapy. Prabu-Jeyabalan M, Nalivaika EA, King NM, Schiffer CA. J Virol 77 1306-1315 (2003)
  6. Mechanism of substrate recognition by drug-resistant human immunodeficiency virus type 1 protease variants revealed by a novel structural intermediate. Prabu-Jeyabalan M, Nalivaika EA, Romano K, Schiffer CA. J Virol 80 3607-3616 (2006)
  7. Crystallographic analysis of human immunodeficiency virus 1 protease with an analog of the conserved CA-p2 substrate -- interactions with frequently occurring glutamic acid residue at P2' position of substrates. Weber IT, Wu J, Adomat J, Harrison RW, Kimmel AR, Wondrak EM, Louis JM. Eur J Biochem 249 523-530 (1997)
  8. Effect of substrate residues on the P2' preference of retroviral proteinases. Boross P, Bagossi P, Copeland TD, Oroszlan S, Louis JM, Tözsér J. Eur J Biochem 264 921-929 (1999)
  9. Crystal structure of HIV-1 protease in situ product complex and observation of a low-barrier hydrogen bond between catalytic aspartates. Das A, Prashar V, Mahale S, Serre L, Ferrer JL, Hosur MV. Proc Natl Acad Sci U S A 103 18464-18469 (2006)
  10. HIV-1 protease variants from 100-fold drug resistant clinical isolates: expression, purification, and crystallization. Vickrey JF, Logsdon BC, Proteasa G, Palmer S, Winters MA, Merigan TC, Kovari LC. Protein Expr Purif 28 165-172 (2003)
  11. Observation of a tetrahedral reaction intermediate in the HIV-1 protease-substrate complex. Kumar M, Prashar V, Mahale S, Hosur MV. Biochem J 389 365-371 (2005)
  12. Role of capsid sequence and immature nucleocapsid proteins p9 and p15 in Human Immunodeficiency Virus type 1 genomic RNA dimerization. Kafaie J, Dolatshahi M, Ajamian L, Song R, Mouland AJ, Rouiller I, Laughrea M. Virology 385 233-244 (2009)
  13. Protocol for rational design of covalently interacting inhibitors. Schmidt TC, Welker A, Rieger M, Sahu PK, Sotriffer CA, Schirmeister T, Engels B. Chemphyschem 15 3226-3235 (2014)
  14. Capturing the reaction pathway in near-atomic-resolution crystal structures of HIV-1 protease. Shen CH, Tie Y, Yu X, Wang YF, Kovalevsky AY, Harrison RW, Weber IT. Biochemistry 51 7726-7732 (2012)
  15. Unexpected novel binding mode of pyrrolidine-based aspartyl protease inhibitors: design, synthesis and crystal structure in complex with HIV protease. Specker E, Böttcher J, Brass S, Heine A, Lilie H, Schoop A, Müller G, Griebenow N, Klebe G. ChemMedChem 1 106-117 (2006)
  16. Deducing hydration sites of a protein from molecular dynamics simulations. Madhusudhan MS, Vishveshwara S. J Biomol Struct Dyn 19 105-114 (2001)
  17. X-ray structure of HIV-1 protease in situ product complex. Bihani S, Das A, Prashar V, Ferrer JL, Hosur MV. Proteins 74 594-602 (2009)
  18. Catalytic water co-existing with a product peptide in the active site of HIV-1 protease revealed by X-ray structure analysis. Prashar V, Bihani S, Das A, Ferrer JL, Hosur M. PLoS One 4 e7860 (2009)


Quick links