PDBsum entry 4b3p

Hydrolase/RNA/DNA

PDB id: 4b3p

Contents

Protein chains

519 a.a.

404 a.a.

DNA/RNA

PDB id:

4b3p

Name:

Hydrolase/RNA/DNA

Title:

Structures of HIV-1 rt and RNA-DNA complex reveal a unique rt conformation and substrate interface

Structure:

Reverse transcriptase/ribonuclease h. Chain: a. Synonym: reverse transcriptase, exoribonuclease h, p66 rt, reverse transcriptase p66 subunit. Ec: 2.7.7.49, 2.7.7.7, 3.1.26.13, 3.4.23.16, 3.1.13.2. Engineered: yes. Mutation: yes. P51 rt. Chain: b.

Source:

Human immunodeficiency virus 1. HIV-1. Organism_taxid: 11676. Expressed in: escherichia coli. Expression_system_taxid: 1007065. Synthetic: yes. Synthetic construct. Organism_taxid: 32630. Organism_taxid: 32630

Resolution:

4.84Å R-factor: 0.366 R-free: 0.404

Authors:

M.Lapkouski,L.Tian,J.T.Miller,S.F.J.Le Grice,W.Yang

Key ref:

M.Lapkouski et al. (2013). Complexes of HIV-1 RT, NNRTI and RNA/DNA hybrid reveal a structure compatible with RNA degradation. Nat Struct Biol, 20, 230-236. PubMed id: 23314251

Date:

25-Jul-12 Release date: 16-Jan-13

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: 519 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: 404 a.a.*

* PDB and UniProt seqs differ at 9 residue positions (black crosses)

DNA/RNA chains

G-T-G-G-T-C-G-T-A-T-G-C-C-T-A-T-A-G-T-T-A 21 bases

U-A-A-C-U-A-U-A-G-G-C-A-U-A-C-G-A-C-C-A-C 21 bases

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

Nat Struct Biol 20:230-236 (2013)

PubMed id: 23314251

Complexes of HIV-1 RT, NNRTI and RNA/DNA hybrid reveal a structure compatible with RNA degradation.

M.Lapkouski, L.Tian, J.T.Miller, S.F.Le Grice, W.Yang.

ABSTRACT

Hundreds of structures of type 1 human immunodeficiency virus (HIV-1) reverse transcriptase (RT) have been determined, but only one contains an RNA/DNA hybrid. Here we report three structures of HIV-1 RT complexed with a non-nucleotide RT inhibitor (NNRTI) and an RNA/DNA hybrid. In the presence of an NNRTI, the RNA/DNA structure differs from all prior nucleic acid-RT structures including the RNA/DNA hybrid. The enzyme structure also differs from all previous RT-DNA complexes. Thus, the hybrid has ready access to the RNase-H active site. These observations indicate that an RT-nucleic acid complex may adopt two structural states, one competent for DNA polymerization and the other for RNA degradation. RT mutations that confer drug resistance but are distant from the inhibitor-binding sites often map to the unique RT-hybrid interface that undergoes conformational changes between two catalytic states.