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PDBsum entry 1vif
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Oxidoreductase PDB id
1vif

 

 

 

 

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Contents
Protein chain
60 a.a.
Ligands
FOL
Waters ×44
PDB id:
1vif
Name: Oxidoreductase
Title: Structure of dihydrofolate reductase
Structure: Dihydrofolate reductase. Chain: a. Synonym: r67 dhfr. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562. Strain: tmp-resistant, containing r67 dhfr overproducing plasmid plz1. Gene: synthetic gene. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Tetramer (from PDB file)
Resolution:
1.80Å     R-factor:   0.176    
Authors: N.Narayana,D.A.Matthews,E.E.Howell,N.-H.Xuong
Key ref: N.Narayana et al. (1995). A plasmid-encoded dihydrofolate reductase from trimethoprim-resistant bacteria has a novel D2-symmetric active site. Nat Struct Biol, 2, 1018-1025. PubMed id: 7583655
Date:
03-Oct-96     Release date:   22-Oct-97    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
P00383  (DYR21_ECOLX) -  Dihydrofolate reductase type 2 from Escherichia coli
Seq:
Struc: 		78 a.a.
60 a.a.
Key:    Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.1.5.1.3  - dihydrofolate reductase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway: 		Folate Coenzymes
      Reaction: (6S)-5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+
(6S)-5,6,7,8-tetrahydrofolate
 + NADP(+)
 =
7,8-dihydrofolate
Bound ligand (Het Group name = FOL)
matches with 40.62% similarity 		+ NADPH
 + H(+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
Nat Struct Biol 2:1018-1025 (1995)
PubMed id: 7583655  
 
 
A plasmid-encoded dihydrofolate reductase from trimethoprim-resistant bacteria has a novel D2-symmetric active site.
N.Narayana, D.A.Matthews, E.E.Howell, X.Nguyen-huu.
 
  ABSTRACT  
 
Bacteria expressing R67-plasmid encoded dihydrofolate reductase (R67 DHFR) exhibit high-level resistance to the antibiotic trimethoprim. Native R67 DHFR is a 34,000 M(r) homotetramer which exists in equilibrium with an inactive dimeric form. The structure of native R67 DHFR has now been solved at 1.7 A resolution and is unrelated to that of chromosomal DHFR. Homotetrameric R67 DHFR has an unusual pore, 25 A in length, passing through the middle of the molecule. Two folate molecules bind asymmetrically within the pore indicating that the enzyme's active site consists of symmetry related binding surfaces from all four identical units.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20410074 E.León, G.Navarro-Avilés, C.M.Santiveri, C.Flores-Flores, M.Rico, C.González, F.J.Murillo, M.Elías-Arnanz, M.A.Jiménez, and S.Padmanabhan (2010).
A bacterial antirepressor with SH3 domain topology mimics operator DNA in sequestering the repressor DNA recognition helix.
  Nucleic Acids Res, 38, 5226-5241.
PDB codes: 2kss 2ksx
18086667 S.Chopra, R.M.Dooling, C.G.Horner, and E.E.Howell (2008).
A balancing act between net uptake of water during dihydrofolate binding and net release of water upon NADPH binding in R67 dihydrofolate reductase.
  J Biol Chem, 283, 4690-4698.  
17371594 A.Verma, and W.Wenzel (2007).
Protein structure prediction by all-atom free-energy refinement.
  BMC Struct Biol, 7, 12.  
17473013 N.Divya, E.Grifith, and N.Narayana (2007).
Structure of the Q67H mutant of R67 dihydrofolate reductase-NADP+ complex reveals a novel cofactor binding mode.
  Protein Sci, 16, 1063-1068.
PDB code: 2p4t
16584884 H.Alonso, and J.E.Gready (2006).
Integron-sequestered dihydrofolate reductase: a recently redeployed enzyme.
  Trends Microbiol, 14, 236-242.  
16790925 N.Narayana (2006).
High-resolution structure of a plasmid-encoded dihydrofolate reductase: pentagonal network of water molecules in the D2-symmetric active site.
  Acta Crystallogr D Biol Crystallogr, 62, 695-706.
PDB code: 2gqv
15812782 E.E.Howell (2005).
Searching sequence space: two different approaches to dihydrofolate reductase catalysis.
  Chembiochem, 6, 590-600.  
16059670 H.Alonso, M.B.Gillies, P.L.Cummins, A.A.Bliznyuk, and J.E.Gready (2005).
Multiple ligand-binding modes in bacterial R67 dihydrofolate reductase.
  J Comput Aided Mol Des, 19, 165-187.  
15148398 A.A.Di Nardo, D.M.Korzhnev, P.J.Stogios, A.Zarrine-Afsar, L.E.Kay, and A.R.Davidson (2004).
Dramatic acceleration of protein folding by stabilization of a nonnative backbone conformation.
  Proc Natl Acad Sci U S A, 101, 7954-7959.  
14691236 H.Fan, and A.E.Mark (2004).
Refinement of homology-based protein structures by molecular dynamics simulation techniques.
  Protein Sci, 13, 211-220.  
14691216 J.Dam, and A.Blondel (2004).
Effect of multiple symmetries on the association of R67 DHFR subunits bearing interfacial complementing mutations.
  Protein Sci, 13, 1.  
15333637 L.G.Stinnett, R.D.Smiley, S.N.Hicks, and E.E.Howell (2004).
"Catch 222," the effects of symmetry on ligand binding and catalysis in R67 dihydrofolate reductase as determined by mutations at Tyr-69.
  J Biol Chem, 279, 47003-47009.  
15333636 S.N.Hicks, R.D.Smiley, L.G.Stinnett, K.H.Minor, and E.E.Howell (2004).
Role of Lys-32 residues in R67 dihydrofolate reductase probed by asymmetric mutations.
  J Biol Chem, 279, 46995-47002.  
12945054 H.Fan, and A.E.Mark (2003).
Relative stability of protein structures determined by X-ray crystallography or NMR spectroscopy: a molecular dynamics simulation study.
  Proteins, 53, 111-120.  
11711548 H.Delbrück, G.Ziegelin, E.Lanka, and U.Heinemann (2002).
An Src homology 3-like domain is responsible for dimerization of the repressor protein KorB encoded by the promiscuous IncP plasmid RP4.
  J Biol Chem, 277, 4191-4198.
PDB codes: 1igq 1igu
12421321 M.F.Feldman, S.Müller, E.Wüest, and G.R.Cornelis (2002).
SycE allows secretion of YopE-DHFR hybrids by the Yersinia enterocolitica type III Ysc system.
  Mol Microbiol, 46, 1183-1197.  
11284680 D.Li, L.A.Levy, S.A.Gabel, M.S.Lebetkin, E.F.DeRose, M.J.Wall, E.E.Howell, and R.E.London (2001).
Interligand Overhauser effects in type II dihydrofolate reductase.
  Biochemistry, 40, 4242-4252.  
11782293 V.Agrawal, and R.K.Kishan (2001).
Functional evolution of two subtly different (similar) folds.
  BMC Struct Biol, 1, 5.  
10736167 F.W.West, H.S.Seo, T.D.Bradrick, and E.E.Howell (2000).
Effects of single-tryptophan mutations on R67 dihydrofolate reductase.
  Biochemistry, 39, 3678-3689.  
10075918 A.Nakagawa, T.Nakashima, M.Taniguchi, H.Hosaka, M.Kimura, and I.Tanaka (1999).
The three-dimensional structure of the RNA-binding domain of ribosomal protein L2; a protein at the peptidyl transferase center of the ribosome.
  EMBO J, 18, 1459-1467.
PDB code: 1rl2
8999931 H.Park, P.Zhuang, R.Nichols, and E.E.Howell (1997).
Mechanistic studies of R67 dihydrofolate reductase. Effects of pH and an H62C mutation.
  J Biol Chem, 272, 2252-2258.  
  8635452 M.A.Martinez, V.Pezo, P.Marlière, and S.Wain-Hobson (1996).
Exploring the functional robustness of an enzyme by in vitro evolution.
  EMBO J, 15, 1203-1210.  
8910413 T.D.Bradrick, C.Shattuck, M.B.Strader, C.Wicker, E.Eisenstein, and E.E.Howell (1996).
Redesigning the quaternary structure of R67 dihydrofolate reductase. Creation of an active monomer from a tetrameric protein by quadruplication of the gene.
  J Biol Chem, 271, 28031-28037.  
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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