1BVG

HIV-1 PROTEASE-DMP323 COMPLEX IN SOLUTION, NMR MINIMIZED AVERAGE STRUCTURE

Summary for 1BVG

• Entry DOI: 10.2210/pdb1bvg/pdb
• Related: 1BVE
• Descriptor: HIV-1 PROTEASE, [4-R-(-4-ALPHA,5-ALPHA,6-BETA,7-BETA)]-HEXAHYDRO-5,6-BIS(HYDROXY)-[1,3-BIS([4-HYDROXYMETHYL-PHENYL]METHYL)-4,7-BIS(PHEN YLMETHYL)]-2H-1,3-DIAZEPINONE (2 entities in total)
• Functional Keywords: aids, polyprotein, hydrolase, aspartyl protease, endonuclease, rna-directed dna polymerase
• Biological source: Human immunodeficiency virus 1
• Cellular location: Matrix protein p17: Virion (Potential). Capsid protein p24: Virion (Potential). Nucleocapsid protein p7: Virion (Potential). Reverse transcriptase/ribonuclease H: Virion (Potential). Integrase: Virion (Potential): P04585
• Total number of polymer chains: 2
• Total formula weight: 22082.02

Authors

Yamazaki, T.,Hinck, A.P.,Wang, Y.-X.,Nicholson, L.K.,Torchia, D.A.,Wingfield, P.,Stahl, S.J.,Kaufman, J.D.,Chang, C.,Domaille, P.J.,Lam, P.Y.S. (deposition date: 1996-01-16, release date: 1996-08-17, Last modification date: 2024-05-22)

Primary citation

Yamazaki, T.,Hinck, A.P.,Wang, Y.X.,Nicholson, L.K.,Torchia, D.A.,Wingfield, P.,Stahl, S.J.,Kaufman, J.D.,Chang, C.H.,Domaille, P.J.,Lam, P.Y.
Three-dimensional solution structure of the HIV-1 protease complexed with DMP323, a novel cyclic urea-type inhibitor, determined by nuclear magnetic resonance spectroscopy.
Protein Sci., 5:495-506, 1996

PubMed Abstract: The three-dimensional solution structure of the HIV-1 protease homodimer, MW 22.2 kDa, complexed to a potent, cyclic urea-based inhibitor, DMP323, is reported. This is the first solution structure of an HIV protease/inhibitor complex that has been elucidated. Multidimensional heteronuclear NMR spectra were used to assemble more than 4,200 distance and angle constraints. Using the constraints, together with a hybrid distance geometry/simulated annealing protocol, an ensemble of 28 NMR structures was calculated having no distance or angle violations greater than 0.3 A or 5 degrees, respectively. Neglecting residues in disordered loops, the RMS deviation (RMSD) for backbone atoms in the family of structures was 0.60 A relative to the average structure. The individual NMR structures had excellent covalent geometry and stereochemistry, as did the restrained minimized average structure. The latter structure is similar to the 1.8-A X-ray structure of the protease/DMP323 complex (Chang CH et al., 1995, Protein Science, submitted); the pairwise backbone RMSD calculated for the two structures is 1.22 A. As expected, the mismatch between the structures is greatest in the loops that are disordered and/or flexible. The flexibility of residues 37-42 and 50-51 may be important in facilitating substrate binding and product release, because these residues make up the respective hinges and tips of the protease flaps. Flexibility of residues 4-8 may play a role in protease regulation by facilitating autolysis.

PubMed: 8868486

Experimental method

SOLUTION NMR