PDBsum entry 1ep4

Transferase

PDB id: 1ep4

Contents

Protein chains

523 a.a. *

395 a.a. *

Ligands

S11

Waters ×197

* Residue conservation analysis

PDB id:

1ep4

Name:

Transferase

Title:

Crystal structure of HIV-1 reverse transcriptase in complex with s- 1153

Structure:

HIV-1 reverse transcriptase. Chain: a. Fragment: p66. Synonym: HIV-1 rt. Engineered: yes. HIV-1 reverse transcriptase. Chain: b. Fragment: p51. Synonym: HIV-1 rt.

Source:

Human immunodeficiency virus 1. Organism_taxid: 11676. Strain: hxb2. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Dimer (from PQS)

Resolution:

2.50Å R-factor: 0.254 R-free: 0.330

Authors:

J.Ren,C.Nichols,L.E.Bird,T.Fujiwara,H.Suginoto,D.I.Stuart, D.K.Stammers

Key ref:

J.Ren et al. (2000). Binding of the second generation non-nucleoside inhibitor S-1153 to HIV-1 reverse transcriptase involves extensive main chain hydrogen bonding. J Biol Chem, 275, 14316-14320. PubMed id: 10799511 DOI: 10.1074/jbc.275.19.14316

Date:

27-Mar-00 Release date: 27-Sep-00

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: 523 a.a.*

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: 395 a.a.

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

Enzyme reactions

• Enzyme class 1: Chains A, B: E.C.2.7.7.- - ?????
• Enzyme class 2: Chains A, B: 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: Chains A, B: 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: Chains A, B: E.C.3.1.-.-
• Enzyme class 5: Chains A, B: 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: Chains A, B: E.C.3.1.26.13 - retroviral ribonuclease H.
• Enzyme class 7: Chains A, B: 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: 10.1074/jbc.275.19.14316

J Biol Chem 275:14316-14320 (2000)

PubMed id: 10799511

Binding of the second generation non-nucleoside inhibitor S-1153 to HIV-1 reverse transcriptase involves extensive main chain hydrogen bonding.

J.Ren, C.Nichols, L.E.Bird, T.Fujiwara, H.Sugimoto, D.I.Stuart, D.K.Stammers.

ABSTRACT

S-1153 (AG1549) is perhaps the most promising non-nucleoside inhibitor of HIV-1 reverse transcriptase currently under development as a potential anti-AIDS drug, because it has a favorable profile of resilience to many drug resistance mutations. We have determined the crystal structure of S-1153 in a complex with HIV-1 reverse transcriptase. The complex possesses some novel features, including an extensive network of hydrogen bonds involving the main chain of residues 101, 103, and 236 of the p66 reverse transcriptase subunit. Such interactions are unlikely to be disrupted by side chain mutations. The reverse transcriptase/S-1153 complex suggests different ways in which resilience to mutations in the non-nucleoside inhibitors of reverse transcriptase binding site can be achieved.

Selected figure(s)

Figure 1.
Fig. 1. Simulated annealing omit electron density map showing the bound S-1153 in the NNRTI pocket of HIV-1 RT. The map is contoured at 3 .

Figure 3.
Fig. 3. Schematic diagram showing the intermolecular interactions between S-1153 and the surrounding residues of HIV-1 RT. The pink spheres represent water molecules in contact with the inhibitor. Residues that contact the NNRTI with a minimum interatomic distance of 3.6Å are shown in green, whereas other residues lining the binding pocket are shown in blue. The individual distances between the NNRTI and the protein atoms are shown as dashed lines (distances less than or equal to 3.3 Å are in pink; distances between 3.3 and 3.6 Å are in light blue; hydrogen bonds are shown together with distances in black).

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2000, 275, 14316-14320) copyright 2000.

Figures were selected by an automated process.