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PDBsum entry 2fxd
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Hydrolase PDB id
2fxd

 

 

 

 

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Contents
Protein chains
99 a.a. *
Ligands
SO4
ACT
DR7
Waters ×193
* Residue conservation analysis
PDB id:
2fxd
Name: Hydrolase
Title: X-ray crystal structure of HIV-1 protease irm mutant complexed with atazanavir (bms-232632)
Structure: Pol protein. Chain: a, b. Fragment: HIV-1 protease. Engineered: yes. Mutation: yes
Source: Human immunodeficiency virus 1. Organism_taxid: 11676. Gene: pol. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Resolution:
1.60Å     R-factor:   0.235     R-free:   0.246
Authors: H.E.Klei,S.Sheriff
Key ref: H.E.Klei et al. (2007). X-ray crystal structures of human immunodeficiency virus type 1 protease mutants complexed with atazanavir. J Virol, 81, 9525-9535. PubMed id: 17537865
Date:
04-Feb-06     Release date:   20-Feb-07    
PROCHECK
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 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q90HG9  (Q90HG9_9HIV1) -  Pol polyprotein (Fragment) from Human immunodeficiency virus 1
Seq:
Struc: 		371 a.a.
99 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 8 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.3.1.26.13  - retroviral ribonuclease H.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

 

 
J Virol 81:9525-9535 (2007)
PubMed id: 17537865  
 
 
X-ray crystal structures of human immunodeficiency virus type 1 protease mutants complexed with atazanavir.
H.E.Klei, K.Kish, P.F.Lin, Q.Guo, J.Friborg, R.E.Rose, Y.Zhang, V.Goldfarb, D.R.Langley, M.Wittekind, S.Sheriff.
 
  ABSTRACT  
 
Atazanavir, which is marketed as REYATAZ, is the first human immunodeficiency virus type 1 (HIV-1) protease inhibitor approved for once-daily administration. As previously reported, atazanavir offers improved inhibitory profiles against several common variants of HIV-1 protease over those of the other peptidomimetic inhibitors currently on the market. This work describes the X-ray crystal structures of complexes of atazanavir with two HIV-1 protease variants, namely, (i) an enzyme optimized for resistance to autolysis and oxidation, referred to as the cleavage-resistant mutant (CRM); and (ii) the M46I/V82F/I84V/L90M mutant of the CRM enzyme, which is resistant to all approved HIV-1 protease inhibitors, referred to as the inhibitor-resistant mutant. In these two complexes, atazanavir adopts distinct bound conformations in response to the V82F substitution, which may explain why this substitution, at least in isolation, has yet to be selected in vitro or in the clinic. Because of its nearly symmetrical chemical structure, atazanavir is able to make several analogous contacts with each monomer of the biological dimer.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20558598 S.K.Law, R.R.Wang, A.N.Mak, K.B.Wong, Y.T.Zheng, and P.C.Shaw (2010).
A switch-on mechanism to activate maize ribosome-inactivating protein for targeting HIV-infected cells.
  Nucleic Acids Res, 38, 6803-6812.  
18281688 J.M.Sayer, F.Liu, R.Ishima, I.T.Weber, and J.M.Louis (2008).
Effect of the active site D25N mutation on the structure, stability, and ligand binding of the mature HIV-1 protease.
  J Biol Chem, 283, 13459-13470.
PDB codes: 3bva 3bvb
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.

 

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