PDBsum entry 1kjh

Hydrolase

PDB id: 1kjh

Contents

Protein chains

99 a.a. *

Ligands

ILE-ARG-LYS-ILE-LEU-PHE-LEU-ASP-GLY-ILE

ACT ×2

Waters ×84

* Residue conservation analysis

PDB id:

1kjh

Name:

Hydrolase

Title:

Substrate shape determines specificity of recognition recognition for HIV-1 protease: analysis of crystal structures of six substrate complexes

Structure:

Pol polyprotein. Chain: a, b. Fragment: HIV-1 protease, residues 57-155. Engineered: yes. Mutation: yes. Pol polyprotein. Chain: p. Fragment: rnase h-integrase substrate peptide, residues 723-732. Engineered: yes

Source:

Human immunodeficiency virus 1. Organism_taxid: 11676. Gene: pol. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes

Biol. unit:

Trimer (from PQS)

Resolution:

2.00Å R-factor: 0.188 R-free: 0.227

Authors:

C.A.Schiffer

Key ref:

M.Prabu-Jeyabalan et al. (2002). Substrate shape determines specificity of recognition for HIV-1 protease: analysis of crystal structures of six substrate complexes. Structure, 10, 369-381. PubMed id: 12005435 DOI: 10.1016/S0969-2126(02)00720-7

Date:

04-Dec-01 Release date: 06-Mar-02

Protein chains

P03369  (POL_HV1A2) -  Gag-Pol polyprotein from Human immunodeficiency virus type 1 group M subtype B (isolate ARV2/SF2)

Seq: 1437 a.a.

Struc: 99 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

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: 10.1016/S0969-2126(02)00720-7

Structure 10:369-381 (2002)

PubMed id: 12005435

Substrate shape determines specificity of recognition for HIV-1 protease: analysis of crystal structures of six substrate complexes.

M.Prabu-Jeyabalan, E.Nalivaika, C.A.Schiffer.

ABSTRACT

The homodimeric HIV-1 protease is the target of some of the most effective antiviral AIDS therapy, as it facilitates viral maturation by cleaving ten asymmetric and nonhomologous sequences in the Gag and Pol polyproteins. Since the specificity of this enzyme is not easily determined from the sequences of these cleavage sites alone, we solved the crystal structures of complexes of an inactive variant (D25N) of HIV-1 protease with six peptides that correspond to the natural substrate cleavage sites. When the protease binds to its substrate and buries nearly 1000 A2 of surface area, the symmetry of the protease is broken, yet most internal hydrogen bonds and waters are conserved. However, no substrate side chain hydrogen bond is conserved. Specificity of HIV-1 protease appears to be determined by an asymmetric shape rather than a particular amino acid sequence.

Selected figure(s)

Figure 4.
Figure 4. Conserved Water Structure(A) Fifty-two water molecules that are conserved in at least four of the five structures determined to 2.0 Å resolution and form at least two protein-hydrogen bonds. Those waters found in both monomers are labeled in bold, and only one of the two is labeled to improve clarity. Equivalent clusters of waters are colored the same. Those waters around the substrate peptide are shown in white (Figure 2). Waters around the P1-loop and the tip of the flap are shown in yellow.(B) On either side of the P1-loop, the conserved waters are shown in blue (C) and red (D). Hydrogen bonds between the protein and water are shown in bold, while hydrogen bonds between nearby protein atoms are shown in dashed lines.

The above figure is reprinted by permission from Cell Press: Structure (2002, 10, 369-381) copyright 2002.

Figure was selected by an automated process.