PDBsum entry 4zhr

Transferase

PDB id: 4zhr

Contents

Protein chains

553 a.a.

409 a.a.

Waters ×38

PDB id:

4zhr

Name:

Transferase

Title:

Structure of HIV-1 rt q151m mutant

Structure:

Rt p66 subunit. Chain: a. Engineered: yes. Mutation: yes. Rt p51 subunit. Chain: b. Engineered: yes. Mutation: yes

Source:

Human immunodeficiency virus 1. HIV-1. Organism_taxid: 11676. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.60Å R-factor: 0.205 R-free: 0.239

Authors:

A.Nakamura,N.Tamura,Y.Yasutake

Key ref:

A.Nakamura et al. (2015). Structure of the HIV-1 reverse transcriptase Q151M mutant: insights into the inhibitor resistance of HIV-1 reverse transcriptase and the structure of the nucleotide-binding pocket of Hepatitis B virus polymerase. Acta Crystallogr F Struct Biol Commun, 71, 1384-1390. PubMed id: 26527265 DOI: 10.1107/S2053230X15017896

Date:

27-Apr-15 Release date: 11-Nov-15

Protein chain

P12497  (POL_HV1N5) -  Gag-Pol polyprotein from Human immunodeficiency virus type 1 group M subtype B (isolate NY5)

Seq: 1435 a.a.

Struc: 553 a.a.*

Protein chain

P12497  (POL_HV1N5) -  Gag-Pol polyprotein from Human immunodeficiency virus type 1 group M subtype B (isolate NY5)

Seq: 1435 a.a.

Struc: 409 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

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: 10.1107/S2053230X15017896

Acta Crystallogr F Struct Biol Commun 71:1384-1390 (2015)

PubMed id: 26527265

Structure of the HIV-1 reverse transcriptase Q151M mutant: insights into the inhibitor resistance of HIV-1 reverse transcriptase and the structure of the nucleotide-binding pocket of Hepatitis B virus polymerase.

A.Nakamura, N.Tamura, Y.Yasutake.

ABSTRACT

Hepatitis B virus polymerase (HBV Pol) is an important target for anti-HBV drug development; however, its low solubility and stability in vitro has hindered detailed structural studies. Certain nucleotide reverse transcriptase (RT) inhibitors (NRTIs) such as tenofovir and lamivudine can inhibit both HBV Pol and Human immunodeficiency virus 1 (HIV-1) RT, leading to speculation on structural and mechanistic analogies between the deoxynucleotide triphosphate (dNTP)-binding sites of these enzymes. The Q151M mutation in HIV-1 RT, located at the dNTP-binding site, confers resistance to various NRTIs, while maintaining sensitivity to tenofovir and lamivudine. The residue corresponding to Gln151 is strictly conserved as a methionine in HBV Pol. Therefore, the structure of the dNTP-binding pocket of the HIV-1 RT Q151M mutant may reflect that of HBV Pol. Here, the crystal structure of HIV-1 RT Q151M, determined at 2.6 Å resolution, in a new crystal form with space group P321 is presented. Although the structure of HIV-1 RT Q151M superimposes well onto that of HIV-1 RT in a closed conformation, a slight movement of the β-strands (β2-β3) that partially create the dNTP-binding pocket was observed. This movement might be caused by the introduction of the bulky thioether group of Met151. The structure also highlighted the possibility that the hydrogen-bonding network among amino acids and NRTIs is rearranged by the Q151M mutation, leading to a difference in the affinity of NRTIs for HIV-1 RT and HBV Pol.