PDBsum entry 1har

Viral protein, transferase

PDB id: 1har

Contents

Protein chain

196 a.a. *

Waters ×90

* Residue conservation analysis

PDB id:

1har

Name:

Viral protein, transferase

Title:

2.2 angstroms resolution structure of the amino-terminal half of HIV-1 reverse transcriptase (fingers and palm subdomains)

Structure:

HIV-1 reverse transcriptase (fingers and palm subdomains). Chain: a. Engineered: yes

Source:

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

Resolution:

2.20Å R-factor: 0.208 R-free: 0.270

Authors:

T.Unge,S.Knight,B.Strandberg

Key ref:

T.Unge et al. (1994). 2.2 A resolution structure of the amino-terminal half of HIV-1 reverse transcriptase (fingers and palm subdomains). Structure, 2, 953-961. PubMed id: 7532533 DOI: 10.1016/S0969-2126(94)00097-2

Date:

28-Oct-94 Release date: 20-Apr-95

Protein chain

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

Seq: 1447 a.a.

Struc: 196 a.a.*

* PDB and UniProt seqs differ at 11 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: 10.1016/S0969-2126(94)00097-2

Structure 2:953-961 (1994)

PubMed id: 7532533

2.2 A resolution structure of the amino-terminal half of HIV-1 reverse transcriptase (fingers and palm subdomains).

T.Unge, S.Knight, R.Bhikhabhai, S.Lövgren, Z.Dauter, K.Wilson, B.Strandberg.

ABSTRACT

BACKGROUND: HIV-1 reverse transcriptase (RT) catalyzes the transformation of single-stranded viral RNA into double-stranded DNA, which is integrated into host cell chromosomes. The molecule is a heterodimer of two subunits, p51 and p66. The amino acid sequence of p51 is identical to the sequence of the amino-terminal subdomains of p66. Earlier crystallographic studies indicate that the RT molecule is flexible, which may explain the difficulty in obtaining high-resolution data for the intact protein. We have therefore determined the structure of a fragment of RT (RT216), which contains only the amino-terminal half of the RT molecule ('finger' and 'palm' subdomains). RESULTS: The crystal structure of RT216 has been refined at 2.2 A resolution to a crystallographic R-value of 20.8%. The structure is very similar to that of the corresponding part of the p66 subunit in the p66/p51 heterodimer, although there is a small difference in the relative orientation of the two subdomains compared with the structure of an RT-DNA-antibody fragment complex. There are a large number of stabilizing contacts (mainly hydrogen bonds and hydrophobic interactions) between the subdomains. The locations of conserved amino acids and the position of some important drug-resistant mutations are described. CONCLUSIONS: The RT216 structure provides detailed three-dimensional information of one important part of HIV-1 RT (including the critical active site residues). We propose a model to explain the inhibitory effect of non-nucleoside inhibitors, which partially accounts for their effect in terms of conformational changes of active site residues.

Selected figure(s)

Figure 2.
Figure 2. The fold of RT216. The names and colours of the subdomains, fingers (blue) and palm (red), and the enumeration of the secondary structure elements follow the nomenclature used for the structure of HIV-1 RT complexed with nevirapine [1] and with DNA and an antibody fragment [5]. The β-strands are marked 0 to 11a and helices are labelled A to F. Two loops which have not been modelled are coloured grey and are located between strands β 3 and β 4 (residues 64–71) and strands β 5a–β 6 (residues 94–104). This drawing and Figure 5 were prepared using the program MOLSCRIPT [22]. Figure 2. The fold of RT216. The names and colours of the subdomains, fingers (blue) and palm (red), and the enumeration of the secondary structure elements follow the nomenclature used for the structure of HIV-1 RT complexed with nevirapine [[3]1] and with DNA and an antibody fragment [[4]5]. The β-strands are marked 0 to 11a and helices are labelled A to F. Two loops which have not been modelled are coloured grey and are located between strands β 3 and β 4 (residues 64–71) and strands β 5a–β 6 (residues 94–104). This drawing and [5]Figure 5 were prepared using the program MOLSCRIPT [[6]22].

Figure 3.
Figure 3. Stereoviews depicting some interactions of particular interest in the RT216 structure. (a) The interface between the palm and the fingers subdomains. The Cαtrace of RT216 is shown together with side chains in the hydrophobic core between the two subdomains. (b) The side chain of Lys73 at the amino terminus of strand β 4 iscompletely buried in a hydrophobic environment where it makes a hydrogen bond to the side chain of Tyr146. This interaction could be important for anchoring the β 3–β 4 loop. Figure 3. Stereoviews depicting some interactions of particular interest in the RT216 structure. (a) The interface between the palm and the fingers subdomains. The Cαtrace of RT216 is shown together with side chains in the hydrophobic core between the two subdomains. (b) The side chain of Lys73 at the amino terminus of strand β 4 iscompletely buried in a hydrophobic environment where it makes a hydrogen bond to the side chain of Tyr146. This interaction could be important for anchoring the β 3–β 4 loop.

The above figures are reprinted by permission from Cell Press: Structure (1994, 2, 953-961) copyright 1994.

Figures were selected by an automated process.