1hsg

File:1hsg.gif

spinqualitylabelsall models PDB ID 1hsg Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image
1hsg, resolution 2.00Å ()
Ligands:
Gene:	HIV-1 PROTEASE FROM THE NY5 ISOLATE (Human immunodeficiency virus 1)
Structural annotation: Resources: CATH : 1Hsga00, 1Hsgb00 InterPro : Ipr010659, Ipr010999, Ipr001995, Ipr008916, Ipr010661, Ipr002156, Ipr001878, Ipr000071, Ipr000721, Ipr012337, Ipr001037, Ipr009007, Ipr001969, Ipr008919, Ipr003308, Ipr000477, Ipr013084, Ipr001584 Pfam : PF00077 SCOP : d1hsga_, d1hsgb_ UniProt : P03367
Functional annotation: Cellular component: cytoplasm viral nucleocapsid nucleus membrane viral capsid virion Biological process: viral reproduction viral procapsid maturation DNA integration proteolysis DNA recombination RNA-dependent DNA replication transposition, DNA-mediated Molecular function: hydrolase activity nucleotidyltransferase activity ribonuclease H activity nucleic acid binding aspartic-type endopeptidase activity peptidase activity endonuclease activity DNA binding transferase activity RNA-directed DNA polymerase activity metal ion binding structural molecule activity RNA binding magnesium ion binding DNA-directed DNA polymerase activity zinc ion binding nuclease activity catalytic activity integrase activity
Evolutionary conservation: Toggle Conservation Colors: Rows = identical sequences: Further Information: Caveats, Explanation, Complete Results at ConSurfDB
Resources:	FirstGlance, OCA, RCSB, PDBsum
Coordinates:	save as pdb, mmCIF, xml

CRYSTAL STRUCTURE AT 1.9 ANGSTROMS RESOLUTION OF HUMAN IMMUNODEFICIENCY VIRUS (HIV) II PROTEASE COMPLEXED WITH L-735,524, AN ORALLY BIOAVAILABLE INHIBITOR OF THE HIV PROTEASES

OverviewOverview

L-735,524 is a potent, orally bioavailable inhibitor of human immunodeficiency virus (HIV) protease currently in a Phase II clinical trial. We report here the three-dimensional structure of L-735,524 complexed to HIV-2 protease at 1.9-A resolution, as well as the structure of the native HIV-2 protease at 2.5-A resolution. The structure of HIV-2 protease is found to be essentially identical to that of HIV-1 protease. In the crystal lattice of the HIV-2 protease complexed with L-735,524, the inhibitor is chelated to the active site of the homodimeric enzyme in one orientation. This feature allows an unambiguous assignment of protein-ligand interactions from the electron density map. Both Fourier and difference Fourier maps reveal clearly the closure of the flap domains of the protease upon L-735,524 binding. Specific interactions between the enzyme and the inhibitor include the hydroxy group of the hydroxyaminopentane amide moiety of L-735,524 ligating to the carboxyl groups of the essential Asp-25 and Asp-25' enzymic residues and the amide oxygens of the inhibitor hydrogen bonding to the backbone amide nitrogen of Ile-50 and Ile-50' via an intervening water molecule. A second bridging water molecule is found between the amide nitrogen N2 of L-735,524 and the carboxyl oxygen of Asp-29'. Although other hydrogen bonds also add to binding, an equally significant contribution to affinity arises from hydrophobic interactions between the protease and the inhibitor throughout the pseudo-symmetric S1/S1', S2/S2', and S3/S3' regions of the enzyme. Except for its pyridine ring, all lipophilic moieties (t-butyl, indanyl, benzyl, and piperidyl) of L-735,524 are rigidly defined in the active site.

About this StructureAbout this Structure

1HSG is a Single protein structure of sequence from Human immunodeficiency virus 1. The following page contains interesting information on the relation of 1HSG with [HIV-1 Protease]. Full crystallographic information is available from OCA.

ReferenceReference

Crystal structure at 1.9-A resolution of human immunodeficiency virus (HIV) II protease complexed with L-735,524, an orally bioavailable inhibitor of the HIV proteases., Chen Z, Li Y, Chen E, Hall DL, Darke PL, Culberson C, Shafer JA, Kuo LC, J Biol Chem. 1994 Oct 21;269(42):26344-8. PMID:7929352 Page seeded by OCA on Fri May 2 19:11:10 2008