PDBsum entry 1a8g

Hydrolase/hydrolase inhibitor

PDB id: 1a8g

Contents

Protein chains

99 a.a. *

Ligands

2Z4

Waters ×69

* Residue conservation analysis

PDB id:

1a8g

Name:

Hydrolase/hydrolase inhibitor

Title:

HIV-1 protease in complex with sdz283-910

Structure:

HIV-1 protease. Chain: a, b. Engineered: yes

Source:

Human immunodeficiency virus 1. Organism_taxid: 11676. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Dimer (from PDB file)

Resolution:

2.50Å R-factor: 0.150 R-free: 0.244

Authors:

J.Kallen,A.Billich,D.Scholz,M.Auer,A.Kungl

Key ref:

S.Ringhofer et al. (1999). X-ray structure and conformational dynamics of the HIV-1 protease in complex with the inhibitor SDZ283-910: agreement of time-resolved spectroscopy and molecular dynamics simulations. J Mol Biol, 286, 1147-1159. PubMed id: 10047488 DOI: 10.1006/jmbi.1998.2533

Date:

24-Mar-98 Release date: 15-Jul-98

Protein chains

P03367  (POL_HV1BR) -  Gag-Pol polyprotein from Human immunodeficiency virus type 1 group M subtype B (isolate BRU/LAI)

Seq: 1447 a.a.

Struc: 99 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class 1: E.C.2.7.7.- - ?????
• Enzyme class 2: E.C.2.7.7.49 - RNA-directed Dna polymerase.
• Reaction: DNA(n) + a 2'-deoxyribonucleoside 5'-triphosphate = DNA(n+1) + diphosphate
• Enzyme class 3: E.C.2.7.7.7 - DNA-directed Dna polymerase.
• Reaction: DNA(n) + a 2'-deoxyribonucleoside 5'-triphosphate = DNA(n+1) + diphosphate
• Enzyme class 4: E.C.3.1.-.-
• Enzyme class 5: E.C.3.1.13.2 - exoribonuclease H.
• Reaction: Exonucleolytic cleavage to 5'-phosphomonoester oligonucleotides in both 5'- to 3'- and 3'- to 5'-directions.
• Enzyme class 6: E.C.3.1.26.13 - retroviral ribonuclease H.
• Enzyme class 7: E.C.3.4.23.16 - HIV-1 retropepsin.
• Reaction: Specific for a P1 residue that is hydrophobic, and P1' variable, but often Pro.

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1006/jmbi.1998.2533

J Mol Biol 286:1147-1159 (1999)

PubMed id: 10047488

X-ray structure and conformational dynamics of the HIV-1 protease in complex with the inhibitor SDZ283-910: agreement of time-resolved spectroscopy and molecular dynamics simulations.

S.Ringhofer, J.Kallen, R.Dutzler, A.Billich, A.J.Visser, D.Scholz, O.Steinhauser, H.Schreiber, M.Auer, A.J.Kungl.

ABSTRACT

Based on the X-ray structure of the human immunodeficiency virus type-1 (HIV-1) protease in complex with the statine-derived inhibitor SDZ283-910, a 542 ps molecular dynamics trajectory was computed. For comparison with the 805 ps trajectory obtained for the uncomplexed enzyme, the theoretical fluorescence anisotropy decay of the unliganded protease and the inhibitor complex was calculated from the trajectories of the Trp6A/Trp6B and Trp42A/Trp42B transition dipole moments. This enabled us to directly compare the simulated data with the experimental picosecond time-resolved fluorescence data. Fitting both experimental and simulated data to the Kohlrausch-Williams-Watts (KWW) function exp(-t/tauk)beta revealed a very good agreement for the uncomplexed protease as well as for the SDZ283-910 complex. Binding of the inhibitor induced a faster decay of both the experimental and the computed protease fluorescence anisotropy decay. By this integrative approach, the atomic detail of inhibitor-induced changes in the conformational dynamics of the HIV-1 protease was experimentally verified and will be used for further inhibitor optimisation.

Selected figure(s)

Figure 1.
Figure 1. Structure of the HIV-1 protease/SDZ283-910 inhibitor complex, indicating the position of the inhibitor as well as of the tryptophan residues.

Figure 2.
Figure 2. Structure of SDZ283-910. Also included are the building blocks used for generating the MD input.

The above figures are reprinted by permission from Elsevier: J Mol Biol (1999, 286, 1147-1159) copyright 1999.

Figures were selected by an automated process.