2PWM

Crystal Structure of HIV-1 CA146 A92E real cell

Summary for 2PWM

• Entry DOI: 10.2210/pdb2pwm/pdb
• Related: 2PWO 2PXR
• Descriptor: Gag-Pol polyprotein, CHLORIDE ION (3 entities in total)
• Functional Keywords: viral capsid, hiv-1, anti-viral, viral protein
• 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 : P12497
• Total number of polymer chains: 8
• Total formula weight: 130384.50

Authors

Kelly, B.N. (deposition date: 2007-05-11, release date: 2007-09-25, Last modification date: 2024-02-21)

Primary citation

Kelly, B.N.,Kyere, S.,Kinde, I.,Tang, C.,Howard, B.R.,Robinson, H.,Sundquist, W.I.,Summers, M.F.,Hill, C.P.
Structure of the Antiviral Assembly Inhibitor CAP-1 Complex with the HIV-1 CA Protein.
J.Mol.Biol., 373:355-366, 2007

PubMed Abstract: The CA domain of the human immunodeficiency virus type 1 (HIV-1) Gag polyprotein plays critical roles in both the early and late phases of viral replication and is therefore an attractive antiviral target. Compounds with antiviral activity were recently identified that bind to the N-terminal domain of CA (CA N) and inhibit capsid assembly during viral maturation. We have determined the structure of the complex between CA N and the antiviral assembly inhibitor N-(3-chloro-4-methylphenyl)-N'-{2-[({5-[(dimethylamino)-methyl]-2-furyl}-methyl)-sulfanyl]ethyl}-urea) (CAP-1) using a combination of NMR spectroscopy and X-ray crystallography. The protein undergoes a remarkable conformational change upon CAP-1 binding, in which Phe32 is displaced from its buried position in the protein core to open a deep hydrophobic cavity that serves as the ligand binding site. The aromatic ring of CAP-1 inserts into the cavity, with the urea NH groups forming hydrogen bonds with the backbone oxygen of Val59 and the dimethylamonium group interacting with the side-chains of Glu28 and Glu29. Elements that could be exploited to improve binding affinity are apparent in the structure. The displacement of Phe32 by CAP-1 appears to be facilitated by a strained main-chain conformation, which suggests a potential role for a Phe32 conformational switch during normal capsid assembly.

PubMed: 17826792
DOI: 10.1016/j.jmb.2007.07.070

Experimental method

X-RAY DIFFRACTION (1.9 Å)