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Q81R22 (Q81R22_BACAN) Unreviewed, UniProtKB/TrEMBL

Last modified April 16, 2014. Version 101. Feed History...

Clusters with 100%, 90%, 50% identity | Third-party data text xml rdf/xml gff fasta
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Names and origin

Protein namesRecommended name:
Dihydrofolate reductase PIRNR PIRNR000194

EC=1.5.1.3 PIRNR PIRNR000194
Gene names
Name:dfrA EMBL AAP26114.1
Ordered Locus Names:BA_2237 EMBL AAP26114.1, BAS2083 EMBL AAT54397.1, GBAA_2237 EMBL AAT31357.1
OrganismBacillus anthracis [Reference proteome] [HAMAP]
Taxonomic identifier1392 [NCBI]
Taxonomic lineageBacteriaFirmicutesBacilliBacillalesBacillaceaeBacillusBacillus cereus group

Protein attributes

Sequence length162 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis By similarity. PIRNR PIRNR000194

Catalytic activity

5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH. PIRNR PIRNR000194

Pathway

Cofactor biosynthesis; tetrahydrofolate biosynthesis; 5,6,7,8-tetrahydrofolate from 7,8-dihydrofolate: step 1/1. PIRNR PIRNR000194

Sequence similarities

Belongs to the dihydrofolate reductase family. RuleBase RU004474 PIRNR PIRNR000194

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Regions

Nucleotide binding19 – 202NADP PDB 3JWM PDB 3JWK PDB 2KGK PDB 3JWF PDB 3DAT PDB 3S9U PDB 3SA2 PDB 3SA1 PDB 3JWC PDB 3JVX PDB 3SAI PDB 3JW5 PDB 3E0B PDB 3JW3
Nucleotide binding45 – 473NADP PDB 3JWM PDB 3JWK PDB 2KGK PDB 3JWF PDB 3DAT PDB 3S9U PDB 3SA2 PDB 3SA1 PDB 3JWC PDB 3JVX PDB 3SAI PDB 3JW5 PDB 3E0B PDB 3JW3
Nucleotide binding63 – 653NADP PDB 3JWM PDB 3JWK PDB 2KGK PDB 3JWF PDB 3DAT PDB 3S9U PDB 3SA2 PDB 3SA1 PDB 3JWC PDB 3JVX PDB 3SAI PDB 3JW5 PDB 3E0B PDB 3JW3
Nucleotide binding98 – 1014NADP PDB 3JWM PDB 3JWK PDB 2KGK PDB 3JWF PDB 3DAT PDB 3S9U PDB 3SA2 PDB 3SA1 PDB 3JWC PDB 3JVX PDB 3SAI PDB 3JW5 PDB 3E0B PDB 3JW3
Region6 – 83Trimethoprim 2 binding
Region6 – 72Methotrexate binding PDB 3DAT PDB 2QK8
Region6 – 72Trimethoprim 1 binding PDB 3JW5
Region6 – 72Trimethoprim 3 binding PDB 3JW3

Sites

Metal binding1081Calcium; via carbonyl oxygen
Metal binding1101Calcium
Metal binding1471Calcium
Binding site81NADP; via amide nitrogen and carbonyl oxygen PDB 3JWM PDB 3JWK PDB 3JWF PDB 3DAT PDB 3S9U PDB 3SA2 PDB 3SA1 PDB 3JWC PDB 3JVX PDB 3SAI PDB 3JW5 PDB 3E0B PDB 3JW3
Binding site151NADP; via carbonyl oxygen PDB 3JWM PDB 3JWK PDB 3JWF PDB 3DAT PDB 3S9U PDB 3SA2 PDB 3SA1 PDB 3JWC PDB 3JVX PDB 3SAI PDB 3JW5 PDB 3E0B PDB 3JW3
Binding site281Methotrexate PDB 3DAT PDB 2QK8
Binding site281Trimethoprim 1 PDB 3JW5
Binding site281Trimethoprim 3 PDB 3JW3
Binding site531Methotrexate PDB 3DAT PDB 2QK8
Binding site581Methotrexate PDB 3DAT PDB 2QK8
Binding site791NADP PDB 2KGK
Binding site961Methotrexate PDB 3DAT PDB 2QK8
Binding site961Trimethoprim 1 PDB 3JW5
Binding site961Trimethoprim 2

Sequences

Sequence LengthMass (Da)Tools
Q81R22 [UniParc].

Last modified June 1, 2003. Version 1.
Checksum: 4259925DD9A1365A

FASTA16219,125
        10         20         30         40         50         60 
MIVSFMVAMD ENRVIGKDNN LPWRLPSELQ YVKKTTMGHP LIMGRKNYEA IGRPLPGRRN 

        70         80         90        100        110        120 
IIVTRNEGYH VEGCEVAHSV EEVFELCKNE EEIFIFGGAQ IYDLFLPYVD KLYITKIHHA 

       130        140        150        160 
FEGDTFFPEM DMTNWKEVFV EKGLTDEKNP YTYYYHVYEK QQ 

« Hide

References

« Hide 'large scale' references
[1]"The genome sequence of Bacillus anthracis Ames and comparison to closely related bacteria."
Read T.D., Peterson S.N., Tourasse N., Baillie L.W., Paulsen I.T., Nelson K.E., Tettelin H., Fouts D.E., Eisen J.A., Gill S.R., Holtzapple E.K., Okstad O.A., Helgason E., Rilstone J., Wu M., Kolonay J.F., Beanan M.J., Dodson R.J. expand/collapse author list , Brinkac L.M., Gwinn M., DeBoy R.T., Madpu R., Daugherty S.C., Durkin A.S., Haft D.H., Nelson W.C., Peterson J.D., Pop M., Khouri H.M., Radune D., Benton J.L., Mahamoud Y., Jiang L., Hance I.R., Weidman J.F., Berry K.J., Plaut R.D., Wolf A.M., Watkins K.L., Nierman W.C., Hazen A., Cline R., Redmond C., Thwaite J.E., White O., Salzberg S.L., Thomason B., Friedlander A.M., Koehler T.M., Hanna P.C., Kolsto A.B., Fraser C.M.
Nature 423:81-86(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: Ames EMBL AAP26114.1 and Ames / isolate Porton.
[2]"Functional cloning of Bacillus anthracis dihydrofolate reductase and confirmation of natural resistance to trimethoprim."
Barrow E.W., Bourne P.C., Barrow W.W.
Antimicrob. Agents Chemother. 48:4643-4649(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE.
Strain: Sterne EMBL AAT40581.1.
[3]"Complete genome sequence of Bacillus anthracis Sterne."
Brettin T.S., Bruce D., Challacombe J.F., Gilna P., Han C., Hill K., Hitchcock P., Jackson P., Keim P., Longmire J., Lucas S., Okinaka R., Richardson P., Rubin E., Tice H.
Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: Sterne EMBL AAT54397.1.
[4]"Crystal structure of the anthrax drug target, Bacillus anthracis dihydrofolate reductase."
Bennett B.C., Xu H., Simmerman R.F., Lee R.E., Dealwis C.G.
J. Med. Chem. 50:4374-4381(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) IN COMPLEX WITH METHOTREXATE.
[5]"Synthetic and crystallographic studies of a new inhibitor series targeting Bacillus anthracis dihydrofolate reductase."
Beierlein J.M., Frey K.M., Bolstad D.B., Pelphrey P.M., Joska T.M., Smith A.E., Priestley N.D., Wright D.L., Anderson A.C.
J. Med. Chem. 51:7532-7540(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) IN COMPLEX WITH NADP.
[6]"Crystal structure of Bacillus anthracis dihydrofolate reductase with the dihydrophthalazine-based trimethoprim derivative RAB1 provides a structural explanation of potency and selectivity."
Bourne C.R., Bunce R.A., Bourne P.C., Berlin K.D., Barrow E.W., Barrow W.W.
Antimicrob. Agents Chemother. 53:3065-3073(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.29 ANGSTROMS) IN COMPLEX WITH CALCIUM AND TRIMETHOPRIM.
[7]"The solution structure of Bacillus anthracis dihydrofolate reductase yields insight into the analysis of structure-activity relationships for novel inhibitors."
Beierlein J.M., Deshmukh L., Frey K.M., Vinogradova O., Anderson A.C.
Biochemistry 48:4100-4108(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR IN COMPLEX WITH NADP.
[8]"The complete genome sequence of Bacillus anthracis Ames 'Ancestor'."
Ravel J., Jiang L., Stanley S.T., Wilson M.R., Decker R.S., Read T.D., Worsham P., Keim P.S., Salzberg S.L., Fraser-Liggett C.M., Rasko D.A.
J. Bacteriol. 191:445-446(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: Ames Ancestor EMBL AAT31357.1 and Ames ancestor.
[9]"X-ray structure of the ternary MTX.NADPH complex of the anthrax dihydrofolate reductase: a pharmacophore for dual-site inhibitor design."
Bennett B.C., Wan Q., Ahmad M.F., Langan P., Dealwis C.G.
J. Struct. Biol. 166:162-171(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) IN COMPLEX WITH METHOTREXATE AND NADP.
[10]"Mutational Studies into Trimethoprim Resistance in Bacillus anthracis Dihydrofolate Reductase."
Beierlein J.M., Karri N.G., Anderson A.C.
Submitted (SEP-2009) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (2.89 ANGSTROMS) IN COMPLEX WITH NADP AND TRIMETHOPRIM.
[11]Joardar V., Shrivastava S., Brinkac L.M., Harkins D.M., Durkin A.S., Sutton G.
Submitted (OCT-2009) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE.
Strain: Ames EMBL AAP26114.1.
[12]"SAR studies of heterocyclic propargyl-linked TMP analogs targeting Bacillus dihydrofolate reductase."
Anderson A.C., Beierlein J.M., Viswanathan K., Wright D.L.
Submitted (JUN-2011) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) IN COMPLEX WITH NADP.
[13]"SAR studies of heterocyclic propargyl-linked TMP analogs to Bacillus dihydrofolate reductase."
Anderson A.C., Beierlein J.M., Viswanathan K., Wright D.L.
Submitted (JUN-2011) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) IN COMPLEX WITH NADP.
[14]"Structure-Activity Studies of Heterocyclic Propargyl-linked TMP Analogs Targeting Bacillus anthracis Dihydrofolate Reductase."
Anderson A.C., Beierlein J.M., Viswanathan K., Wright D.L.
Submitted (JUN-2011) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEX WITH NADP.
[15]"Structure-activity relationship for enantiomers of potent inhibitors of B. anthracis dihydrofolate reductase."
Bourne C.R., Wakeham N., Nammalwar B., Tseitin V., Bourne P.C., Barrow E.W., Mylvaganam S., Ramnarayan K., Bunce R.A., Berlin K.D., Barrow W.W.
Biochim. Biophys. Acta 1834:46-52(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS).

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AE016879 Genomic DNA. Translation: AAP26114.1.
AE017334 Genomic DNA. Translation: AAT31357.1.
AY569129 Genomic DNA. Translation: AAT40581.1.
AE017225 Genomic DNA. Translation: AAT54397.1.
RefSeqNP_844628.1. NC_003997.3.
YP_018882.1. NC_007530.2.
YP_028346.1. NC_005945.1.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2KGKNMR-A1-162[»]
2QK8X-ray2.40A1-162[»]
3DATX-ray2.30A1-162[»]
3E0BX-ray2.25A/B1-162[»]
3FL8X-ray2.29A/B/C/D/E/F/G/H1-162[»]
3FL9X-ray2.40A/B/C/D/E/F/G/H1-162[»]
3JVXX-ray2.25A/B1-162[»]
3JW3X-ray2.57A/B1-162[»]
3JW5X-ray2.89A/B1-162[»]
3JWCX-ray2.57A/B1-162[»]
3JWFX-ray2.57A/B1-162[»]
3JWKX-ray2.08A/B1-162[»]
3JWMX-ray2.57A/B1-162[»]
3S9UX-ray1.90A/B1-162[»]
3SA1X-ray2.50A/B1-162[»]
3SA2X-ray2.25A/B1-162[»]
3SAIX-ray2.25A/B1-162[»]
4ELBX-ray2.60A/B/C/D/E/F/G/H1-162[»]
4ELEX-ray2.35A/B/C/D/E/F/G/H1-162[»]
4ELFX-ray2.30A/B/C/D/E/F/G/H1-162[»]
4ELGX-ray2.10A/B/C/D/E/F/G/H1-162[»]
4ELHX-ray2.10A/B/C/D/E/F/G/H1-162[»]
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING198094.BA_2237.

Chemistry

ChEMBLCHEMBL5270.

Protocols and materials databases

DNASU1085515.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaAAP26114; AAP26114; BA_2237.
AAT31357; AAT31357; GBAA_2237.
AAT54397; AAT54397; BAS2083.
GeneID1085515.
2814627.
2849969.
KEGGban:BA_2237.
bar:GBAA_2237.
bat:BAS2083.

Phylogenomic databases

KOK00287.
OMADTQFPDW.
OrthoDBEOG6KT2V2.
ProtClustDBCLSK916541.

Enzyme and pathway databases

BioCycANTHRA:DFRA-MONOMER.
BANT260799:GJAJ-2151-MONOMER.
BANT261594:GJ7F-2226-MONOMER.
UniPathwayUPA00077; UER00158.

Family and domain databases

Gene3D3.40.430.10. 1 hit.
InterProIPR012259. DHFR.
IPR024072. DHFR-like_dom.
IPR017925. DHFR_CS.
IPR001796. DHFR_dom.
[Graphical view]
PfamPF00186. DHFR_1. 1 hit.
[Graphical view]
PIRSFPIRSF000194. DHFR. 1 hit.
PRINTSPR00070. DHFR.
SUPFAMSSF53597. SSF53597. 1 hit.
PROSITEPS00075. DHFR_1. 1 hit.
PS51330. DHFR_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ81R22.

Entry information

Entry nameQ81R22_BACAN
AccessionPrimary (citable) accession number: Q81R22
Secondary accession number(s): E9R6R2 expand/collapse secondary AC list , E9R6R3, E9R6R4, Q68SA0, Q6HZ92, Q6KT86
Entry history
Integrated into UniProtKB/TrEMBL: June 1, 2003
Last sequence update: June 1, 2003
Last modified: April 16, 2014
This is version 101 of the entry and version 1 of the sequence. [Complete history]
Entry statusUnreviewed (UniProtKB/TrEMBL)