4HVP

Structure of complex of synthetic HIV-1 protease with a substrate-based inhibitor at 2.3 Angstroms resolution

Summary for 4HVP

• Entry DOI: 10.2210/pdb4hvp/pdb
• Related PRD ID: PRD_000398
• Descriptor: HIV-1 PROTEASE, N-{(2S)-2-[(N-acetyl-L-threonyl-L-isoleucyl)amino]hexyl}-L-norleucyl-L-glutaminyl-N~5~-[amino(iminio)methyl]-L-ornithinamide (3 entities in total)
• Functional Keywords: acid proteinase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Human immunodeficiency virus 1
• 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 : P03369
• Total number of polymer chains: 2
• Total formula weight: 22300.26

Authors

Miller, M.,Schneider, J.,Sathyanarayana, B.K.,Toth, M.V.,Marshall, G.R.,Clawson, L.,Selk, L.,Kent, S.B.H.,Wlodawer, A. (deposition date: 1989-08-08, release date: 1990-04-15, Last modification date: 2025-03-26)

Primary citation

Miller, M.,Schneider, J.,Sathyanarayana, B.K.,Toth, M.V.,Marshall, G.R.,Clawson, L.,Selk, L.,Kent, S.B.,Wlodawer, A.
Structure of complex of synthetic HIV-1 protease with a substrate-based inhibitor at 2.3 A resolution.
Science, 246:1149-1152, 1989

PubMed Abstract: The structure of a complex between a peptide inhibitor with the sequence N-acetyl-Thr-Ile-Nle-psi[CH2-NH]-Nle-Gln-Arg.amide (Nle, norleucine) with chemically synthesized HIV-1 (human immunodeficiency virus 1) protease was determined at 2.3 A resolution (R factor of 0.176). Despite the symmetric nature of the unliganded enzyme, the asymmetric inhibitor lies in a single orientation and makes extensive interactions at the interface between the two subunits of the homodimeric protein. Compared with the unliganded enzyme, the protein molecule underwent substantial changes, particularly in an extended region corresponding to the "flaps" (residues 35 to 57 in each chain), where backbone movements as large as 7 A are observed.

PubMed: 2686029

Experimental method

X-RAY DIFFRACTION (2.3 Å)