PDBsum entry 1a9m

Aspartyl protease

PDB id: 1a9m

Contents

Protein chains

99 a.a. *

Ligands

U0E

Waters ×59

* Residue conservation analysis

PDB id:

1a9m

Name:

Aspartyl protease

Title:

G48h mutant of HIV-1 protease in complex with a peptidic inhibitor u- 89360e

Structure:

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

Source:

Human immunodeficiency virus 1. Organism_taxid: 11676. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.

Biol. unit:

Tetramer (from PQS)

Resolution:

2.30Å R-factor: 0.185

Authors:

L.Hong,X.-J.Zhang,S.Foundling,J.A.Hartsuck,J.Tang

Key ref:

L.Hong et al. (1997). Structure of a G48H mutant of HIV-1 protease explains how glycine-48 replacements produce mutants resistant to inhibitor drugs. Febs Lett, 420, 11-16. PubMed id: 9450540 DOI: 10.1016/S0014-5793(97)01477-4

Date:

08-Apr-98 Release date: 17-Jun-98

Protein chains

P03366  (POL_HV1B1) -  Gag-Pol polyprotein from Human immunodeficiency virus type 1 group M subtype B (isolate BH10)

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: 10.1016/S0014-5793(97)01477-4

Febs Lett 420:11-16 (1997)

PubMed id: 9450540

Structure of a G48H mutant of HIV-1 protease explains how glycine-48 replacements produce mutants resistant to inhibitor drugs.

L.Hong, X.J.Zhang, S.Foundling, J.A.Hartsuck, J.Tang.

ABSTRACT

The crystal structure of human immunodeficiency virus type 1 (HIV-1) protease mutant G48H with peptidic inhibitor U-89360E is described. Comparison with wild-type protease-inhibitor complex shows that mutation of flap residue 48 to histidine allows stabilizing van der Waals contacts between the side chains of His48 and Phe53 as well as between His48 and the P2' and P3' inhibitor subsites. The flap region is less mobile than in the wild-type enzyme. A model of saquinavir-resistant mutant protease G48V in complex with saquinavir predicts interactions similar to those found in the G48H crystal. Energetic calculations confirm the similarity of the His48 and Val48 interactions.

Selected figure(s)

Figure 2.
Fig. 2. Stereo view of the structural relationship of the inhibitor molecule and protease residues 48A, 53A, 48B and 53B. Electron densities from the 2|F[o]|−|F[c]| map are shown at 1 σ contour level. A C[α] to C[α] backbone trace for residues 48 to 53 is included. The position of the side chain of residue B53 in the wild-type structure is also shown (orange).

Figure 4.
Fig. 4. Van der Waals interaction of Phe^A53, Val^A48 and the P[3] subsite of saquinavir in the structural model of HIV-1 mutant protease G48V complex with saquinavir. The saquinavir positions in the wild-type crystal structure (orange) and of the G48V mutant model structure (yellow) are both shown. There is a 30° rotation of the saquinavir P[3] planar quinoline group (double ring) in the G48V complex compared to that in the wild-type enzyme. This change appears to be a result of its interaction with Val^48. The van der Waals interaction between Val^48 and Phe^53 is shown but the view does not minimize overlap of the surfaces.

The above figures are reprinted by permission from the Federation of European Biochemical Societies: Febs Lett (1997, 420, 11-16) copyright 1997.

Figures were selected by an automated process.