Annotation for this protein is in progress - please check future releases for more complete information


DP00301: Dihydrofolate reductaseFASTA viewXML view

General information
DisProt:DP00301
Name:Dihydrofolate reductase
Synonym(s):DYR_ECOLI
EC 1.5.1.3
DHFR
First appeared in release:Release 3.0 (02/17/2006)
UniProt:P0ABQ4
UniGene: 
SwissProt: DYR_ECOLI
TrEMBL:  
NCBI (GI): 81175282
Source organism:Escherichia coli
Sequence length:159
Percent disordered:34%
Homologues: 


Native sequence

        10         20         30         40         50         60
         |          |          |          |          |          |
MISLIAALAV DRVIGMENAM PWNLPADLAW FKRNTLNKPV IMGRHTWESI GRPLPGRKNI - 60
ILSSQPGTDD RVTWVKSVDE AIAACGDVPE IMVIGGGRVY EQFLPKAQKL YLTHIDAEVE - 120
GDTHFPDYEP DDWESVFSEF HDADAQNSHS YCFEILERR

Region 5: 16-20 Region 4: 63-72 Region 6: 95-96 Region 2: 116-132 Region 3: 142-150 Region 7: 16-22 Region 1: 9-24

Map of ordered and disordered regions







Note: 'Mouse' over a region to see the start and stop residues. Click on a region to see detailed information.


Region 3
Type:Disordered
Name:G-H loop
Location:142 - 150
Length:9
Region sequence:

DADAQNSHS

Modification type: Complex
PDB: 1DDS:A, 1DDS:B, 1DDR:A, 1DDR:B
Structural/functional type: Function arises via a disorder to order transition
Functional classes:  
Functional subclasses: Substrate/ligand binding
Detection methods:
  1. X-ray crystallography
References:
  1. Sawaya MR, Kraut J. "Loop and subdomain movements in the mechanism of Escherichia coli dihydrofolate reductase: crystallographic evidence." Biochemistry. 1997; 36(3): 586-603. PubMed: 9012674

  2. Schnell JR, Dyson HJ, Wright PE. "Effect of cofactor binding and loop conformation on side chain methyl dynamics in dihydrofolate reductase." Biochemistry. 2004; 43(2): 374-83. PubMed: 14717591
Comments:
 



Region 2
Type:Disordered
Name:F-G loop
Location:116 - 132
Length:17
Region sequence:

DAEVEGDTHFPDYEPDD

Modification type: Complex
PDB: 1DDS:A, 1DDS:B, 1DDR:A, 1DDR:B
Structural/functional type: Function arises via a disorder to order transition
Functional classes:  
Functional subclasses: Substrate/ligand binding
Detection methods:
  1. X-ray crystallography
References:
  1. Sawaya MR, Kraut J. "Loop and subdomain movements in the mechanism of Escherichia coli dihydrofolate reductase: crystallographic evidence." Biochemistry. 1997; 36(3): 586-603. PubMed: 9012674

  2. Schnell JR, Dyson HJ, Wright PE. "Effect of cofactor binding and loop conformation on side chain methyl dynamics in dihydrofolate reductase." Biochemistry. 2004; 43(2): 374-83. PubMed: 14717591
Comments:
 



Region 1
Type:Disordered
Name:Met20 loop
Location:9 - 24
Length:16
Region sequence:

AVDRVIGMENAMPWNL

Modification type: Complex
PDB: 1DDS:A, 1DDS:B, 1DDR:A, 1DDR:B
Structural/functional type: Function arises via a disorder to order transition
Functional classes:  
Functional subclasses: Substrate/ligand binding
Detection methods:
  1. X-ray crystallography
References:
  1. Sawaya MR, Kraut J. "Loop and subdomain movements in the mechanism of Escherichia coli dihydrofolate reductase: crystallographic evidence." Biochemistry. 1997; 36(3): 586-603. PubMed: 9012674

  2. Schnell JR, Dyson HJ, Wright PE. "Effect of cofactor binding and loop conformation on side chain methyl dynamics in dihydrofolate reductase." Biochemistry. 2004; 43(2): 374-83. PubMed: 14717591
Comments:
 



Region 7
Type:Disordered
Name:Met20 loop
Location:16 - 22
Length:7
Region sequence:

MENAMPW

Modification type: Complex
PDB: 1RG7:A
Structural/functional type: Function arises via a disorder to order transition
Functional classes: Molecular assembly
Functional subclasses: Substrate/ligand binding
Detection methods:
  1. X-ray crystallography (CaCl2 50 mM; imidazole (pH 7.0) 20 mM; imidazole (second aliquot) (pH 7.2) 60 mM; PEG 6000 (w/v) 25 %)
References:
  1. Sawaya MR, Kraut J. "Loop and subdomain movements in the mechanism of Escherichia coli dihydrofolate reductase: crystallographic evidence." Biochemistry. 1997; 36(3): 586-603. PubMed: 9012674

  2. Schnell JR, Dyson HJ, Wright PE. "Effect of cofactor binding and loop conformation on side chain methyl dynamics in dihydrofolate reductase." Biochemistry. 2004; 43(2): 374-83. PubMed: 14717591
Comments:
 



Region 6
Type:Disordered
Name: 
Location:95 - 96
Length:2
Region sequence:

GG

Modification type: Complex
PDB: 5DFR:A
Structural/functional type: Relationship to function unknown
Functional classes: Unknown
Functional subclasses: Unknown
Detection methods:
  1. X-ray crystallography (277 K; )
References:
  1. Sawaya MR, Kraut J. "Loop and subdomain movements in the mechanism of Escherichia coli dihydrofolate reductase: crystallographic evidence." Biochemistry. 1997; 36(3): 586-603. PubMed: 9012674

  2. Schnell JR, Dyson HJ, Wright PE. "Effect of cofactor binding and loop conformation on side chain methyl dynamics in dihydrofolate reductase." Biochemistry. 2004; 43(2): 374-83. PubMed: 14717591
Comments:
 



Region 5
Type:Disordered
Name:Met20 loop
Location:16 - 20
Length:5
Region sequence:

MENAM

Modification type: Complex
PDB: 5DFR:A, 6DFR:A
Structural/functional type: Function arises via a disorder to order transition
Functional classes: Molecular assembly
Functional subclasses: Substrate/ligand binding
Detection methods:
  1. X-ray crystallography (277 K; DHFR (40 to 50 mg/ml))

  2. X-ray crystallography (298 K; CaCl2 50 mM; imidazole (pH 7.0) 20 mM; imidazole (second aliquot) (pH 7.2) 60 mM; PEG 6000 ((w/v)) 25 %)
References:
  1. Sawaya MR, Kraut J. "Loop and subdomain movements in the mechanism of Escherichia coli dihydrofolate reductase: crystallographic evidence." Biochemistry. 1997; 36(3): 586-603. PubMed: 9012674

  2. Schnell JR, Dyson HJ, Wright PE. "Effect of cofactor binding and loop conformation on side chain methyl dynamics in dihydrofolate reductase." Biochemistry. 2004; 43(2): 374-83. PubMed: 14717591
Comments:
PDB ID 5DFR had V10, L28, E120, D122, and D127 containing disordered side chains.

PDB ID 6DFR had the side chains beyond the CB of E120 and D127 being disordered.


Region 4
Type:Disordered
Name: 
Location:63 - 72
Length:10
Region sequence:

SSQPGTDDRV

Modification type: Complex
PDB: 1DDR:A, 1DDR:B, 1DDS:A, 1DDS:B
Structural/functional type: Function arises via a disorder to order transition
Functional classes: Unknown
Functional subclasses: Unknown
Detection methods:
  1. X-ray crystallography
References:
  1. Sawaya MR, Kraut J. "Loop and subdomain movements in the mechanism of Escherichia coli dihydrofolate reductase: crystallographic evidence." Biochemistry. 1997; 36(3): 586-603. PubMed: 9012674

  2. Schnell JR, Dyson HJ, Wright PE. "Effect of cofactor binding and loop conformation on side chain methyl dynamics in dihydrofolate reductase." Biochemistry. 2004; 43(2): 374-83. PubMed: 14717591
Comments:
 



References

  1. Smith DR, Calvo JM. "Nucleotide sequence of the E coli gene coding for dihydrofolate reductase." Nucleic Acids Res. 1980; 8(10): 2255-74. PubMed: 6159575

  2. Venkitakrishnan RP, Zaborowski E, McElheny D, Benkovic SJ, Dyson HJ, Wright PE. "Conformational changes in the active site loops of dihydrofolate reductase during the catalytic cycle." Biochemistry. 2004; 43(51): 16046-55. PubMed: 15609999


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