3DOX

X-ray structure of HIV-1 protease in situ product complex

Summary for 3DOX

• Entry DOI: 10.2210/pdb3dox/pdb
• Related: 1G6L 1LV1 2NPH
• Descriptor: HIV-1 PROTEASE, A PEPTIDE SUBSTRATE-SQNY, A PEPTIDE SUBSTRATE-PIV, ... (4 entities in total)
• Functional Keywords: hiv-1 protease; transition state; reaction intermediate; catalysis; inhibitor; x-ray crystallography, aids, aspartyl protease, capsid maturation, capsid protein, cytoplasm, dna integration, dna recombination, dna-directed dna polymerase, endonuclease, host-virus interaction, hydrolase, lipoprotein, magnesium, metal-binding, multifunctional enzyme, myristate, nuclease, nucleotidyltransferase, nucleus, phosphoprotein, protease, ribosomal frameshifting, rna-binding, rna-directed dna polymerase, transferase, viral nucleoprotein, virion, zinc, zinc-finger
• Biological source: Human immunodeficiency virus type 1 (isolate HXB2 group M subtype B) (HIV-1, HIV-1 M:B_HXB2R); More
• Cellular location: Gag-Pol polyprotein: Host cell membrane; Lipid-anchor . Matrix protein p17: Virion membrane; Lipid- anchor . Capsid protein p24: Virion . Nucleocapsid protein p7: Virion . Reverse transcriptase/ribonuclease H: Virion . Integrase: Virion : P04585
• Total number of polymer chains: 3
• Total formula weight: 22740.68

Authors

Hosur, M.V.,Ferrer, J.-L.,Das, A.,Prashar, V.,Bihani, S. (deposition date: 2008-07-07, release date: 2008-09-09, Last modification date: 2024-05-29)

Primary citation

Bihani, S.,Das, A.,Prashar, V.,Ferrer, J.-L.,Hosur, M.V.
X-ray structure of HIV-1 protease in situ product complex
Proteins, 74:594-602, 2009

PubMed Abstract: HIV-1 protease is an effective target for design of different types of drugs against AIDS. HIV-1 protease is also one of the few enzymes that can cleave substrates containing both proline and nonproline residues at the cleavage site. We report here the first structure of HIV-1 protease complexed with the product peptides SQNY and PIV derived by in situ cleavage of the oligopeptide substrate SQNYPIV, within the crystals. In the structure, refined against 2.0-A resolution synchrotron data, a carboxyl oxygen of SQNY is hydrogen-bonded with the N-terminal nitrogen atom of PIV. At the same time, this proline nitrogen atom does not form any hydrogen bond with catalytic aspartates. These two observations suggest that the protonation of scissile nitrogen, during peptide bond cleavage, is by a gem-hydroxyl of the tetrahedral intermediate rather than by a catalytic aspartic acid.

PubMed: 18704947
DOI: 10.1002/prot.22174

Experimental method

X-RAY DIFFRACTION (2 Å)