PDBsum entry 3dox

Hydrolase

PDB id: 3dox

Contents

Protein chain

198 a.a. *

Ligands

SER-GLN-ASN-TYR

PRO-ILE-VAL

Waters ×193

* Residue conservation analysis

PDB id:

3dox

Name:

Hydrolase

Title:

X-ray structure of HIV-1 protease in situ product complex

Structure:

HIV-1 protease. Chain: a. Synonym: pr160gag-pol, matrix protein p17, ma, capsid protein p24, ca, spacer peptide p2, nucleocapsid protein p7, nc, transframe peptide, tf, p6-pol, p6 , Protease, retropepsin, pr, reverse transcriptase/ribonuclease h, p66 rt, p51 rt, p15, integrase, in. Engineered: yes. Mutation: yes. Other_details: tethered dimer linked by ggssg.

Source:

Human immunodeficiency virus type 1 (isolate hxb2 group m subtype b). HIV-1, HIV-1 m:b_hxb2r. Organism_taxid: 11706. Gene: gag-pol. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: the peptide was chemically synthesized..

Resolution:

2.00Å R-factor: 0.197 R-free: 0.236

Authors:

M.V.Hosur,J.-L.Ferrer,A.Das,V.Prashar,S.Bihani

Key ref:

S.Bihani et al. (2008). X-ray structure of HIV-1 protease in situ product complex. Proteins, 74, 594-602. PubMed id: 18704947 DOI: 10.1002/prot.22174

Date:

07-Jul-08 Release date: 09-Sep-08

Protein chain

P04585  (POL_HV1H2) -  Gag-Pol polyprotein from Human immunodeficiency virus type 1 group M subtype B (isolate HXB2)

Seq: 1435 a.a.

Struc: 198 a.a.*

* PDB and UniProt seqs differ at 93 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: 10.1002/prot.22174

Proteins 74:594-602 (2008)

PubMed id: 18704947

X-ray structure of HIV-1 protease in situ product complex.

S.Bihani, A.Das, V.Prashar, J.L.Ferrer, M.V.Hosur.

ABSTRACT

HIV-1 protease is an effective target for design of different types of drugs against AIDS. HIV-1 protease is also one of the few enzymes that can cleave substrates containing both proline and nonproline residues at the cleavage site. We report here the first structure of HIV-1 protease complexed with the product peptides SQNY and PIV derived by in situ cleavage of the oligopeptide substrate SQNYPIV, within the crystals. In the structure, refined against 2.0-A resolution synchrotron data, a carboxyl oxygen of SQNY is hydrogen-bonded with the N-terminal nitrogen atom of PIV. At the same time, this proline nitrogen atom does not form any hydrogen bond with catalytic aspartates. These two observations suggest that the protonation of scissile nitrogen, during peptide bond cleavage, is by a gem-hydroxyl of the tetrahedral intermediate rather than by a catalytic aspartic acid. Proteins 2009. (c) 2008 Wiley-Liss, Inc.

Selected figure(s)

Figure 2.
Figure 2. Stereodiagram superposing present structure (yellow carbon) with the structure of hydroxy-inhibitor (JG365) complex(green) [PDB ID 2J9J]. The putative catalytic water H4 (orange sphere) is at 1.4 Å from the hydroxyl oxygen of the inhibitor. The flap water molecules (FW) for the two structures are also drawn.

Figure 3.
Figure 3. Hydrogen bonding interactions: (A) in the active site cavity. Full occupancy water molecules are shown as green spheres. Partial occupancy water molecules are shown as red spheres. Hydrogen bonds between partial water molecules are drawn in purple. (B) involving P1, P1 , H4, and catalytic aspartate residues. Interatomic distances are given in Å units.

The above figures are reprinted by permission from John Wiley & Sons, Inc.: Proteins (2008, 74, 594-602) copyright 2008.

Figures were selected by an automated process.