Q81R22 (Q81R22_BACAN) Unreviewed, UniProtKB/TrEMBL

Names and origin

Protein names

Recommended 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

Organism

Bacillus anthracis [Reference proteome] [HAMAP]

Taxonomic identifier

1392 [NCBI]

Taxonomic lineage

cellular organisms › Bacteria › Firmicutes › Bacilli › Bacillales › Bacillaceae › Bacillus › Bacillus cereus group

Protein attributes

Sequence length	162 AA.
Sequence status	Complete.
Protein existence	Evidence 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. PIRNR PIRNR000194
Sequence similarities	Belongs to the dihydrofolate reductase family. RuleBase RU004474 PIRNR PIRNR000194

Ontologies

Keywords
Biological process	One-carbon metabolism PIRNR PIRNR000194
Ligand	Calcium PDB 3FL9 Metal-binding PDB 3FL9 NADP PIRNR PIRNR000194 PDB 3JWM PDB 3JWK PDB 3JWF PDB 2KGK PDB 3DAT PDB 3JWC PDB 3JVX PDB 3E0B PDB 3JW5 PDB 3JW3 Nucleotide-binding PDB 3JWM PDB 3JWK PDB 3JWF PDB 2KGK PDB 3DAT PDB 3JWC PDB 3JVX PDB 3E0B PDB 3JW5 PDB 3JW3
Molecular function	Oxidoreductase PIRNR PIRNR000194 EMBL AAP26114.1
Technical term	3D-structure PDB 3FL9 PDB 3JWM PDB 4ELB PDB 3JWK PDB 4ELE PDB 3JWF PDB 2KGK PDB 4ELF PDB 3DAT PDB 4ELG PDB 3S9U PDB 4ELH PDB 3SA2 PDB 3SA1 PDB 3JWC PDB 3JVX PDB 3SAI PDB 3E0B PDB 3JW5 PDB 2QK8 PDB 3FL8 PDB 3JW3 Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	glycine biosynthetic process Inferred from electronic annotation. Source: InterPro nucleotide biosynthetic process Inferred from electronic annotation. Source: InterPro one-carbon metabolic process Inferred from electronic annotation. Source: UniProtKB-KW tetrahydrofolate biosynthetic process Inferred from electronic annotation. Source: UniProtKB-UniPathway
Molecular_function	NADP binding Inferred from electronic annotation. Source: InterPro dihydrofolate reductase activity Inferred from electronic annotation. Source: EC metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Regions
	Nucleotide binding	19 – 20	2	NADP PDB 2KGK
	Nucleotide binding	45 – 47	3	NADP PDB 2KGK
	Nucleotide binding	63 – 65	3	NADP PDB 2KGK
	Nucleotide binding	98 – 101	4	NADP PDB 2KGK
	Region	6 – 8	3	Trimethoprim 2 binding PDB 3FL9
	Region	6 – 7	2	Methotrexate binding PDB 2QK8
	Region	6 – 7	2	Trimethoprim 1 binding PDB 3JW5
	Region	6 – 7	2	Trimethoprim 3 binding PDB 3JW3
Sites
	Metal binding	108	1	Calcium; via carbonyl oxygen PDB 3FL9
	Metal binding	110	1	Calcium PDB 3FL9
	Metal binding	147	1	Calcium PDB 3FL9
	Binding site	8	1	NADP; via amide nitrogen and carbonyl oxygen
	Binding site	15	1	NADP; via carbonyl oxygen
	Binding site	28	1	Methotrexate PDB 2QK8
	Binding site	28	1	Trimethoprim 1 PDB 3JW5
	Binding site	28	1	Trimethoprim 3 PDB 3JW3
	Binding site	53	1	Methotrexate PDB 2QK8
	Binding site	58	1	Methotrexate PDB 2QK8
	Binding site	79	1	NADP PDB 2KGK
	Binding site	96	1	Methotrexate PDB 2QK8
	Binding site	96	1	Trimethoprim 1 PDB 3JW5
	Binding site	96	1	Trimethoprim 2 PDB 3FL9

Sequences

	Sequence		Length	Mass (Da)
	Q81R22 [UniParc]. Last modified June 1, 2003. Version 1. Checksum: 4259925DD9A1365A	FASTA	162	19,125
	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

References

	« Hide 'large scale' referencesShow '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.J., 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. , Brinkac L.M., Gwinn M.L., 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.T., Redmond C., Thwaite J.E., White O., Salzberg S.L., Thomason B., Friedlander A.M., Koehler T.M., Hanna P.C., Kolstoe 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) OF 3-162 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) OF 3-162 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) OF 3-162.
[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) OF 3-162.
[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) OF 3-162.
[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.

RefSeq

NP_844628.1. NC_003997.3.
YP_018882.1. NC_007530.2.
YP_028346.1. NC_005945.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2KGK	NMR	-	A	1-162	[»]
2QK8	X-ray	2.40	A	1-162	[»]
3DAT	X-ray	2.30	A	1-162	[»]
3E0B	X-ray	2.25	A/B	3-162	[»]
3FL8	X-ray	2.29	A/B/C/D/E/F/G/H	1-162	[»]
3FL9	X-ray	2.40	A/B/C/D/E/F/G/H	1-162	[»]
3JVX	X-ray	2.25	A/B	3-162	[»]
3JW3	X-ray	2.57	A/B	3-162	[»]
3JW5	X-ray	2.89	A/B	3-162	[»]
3JWC	X-ray	2.57	A/B	3-162	[»]
3JWF	X-ray	2.57	A/B	3-162	[»]
3JWK	X-ray	2.08	A/B	3-162	[»]
3JWM	X-ray	2.57	A/B	3-162	[»]
3S9U	X-ray	1.90	A/B	3-162	[»]
3SA1	X-ray	2.50	A/B	3-162	[»]
3SA2	X-ray	2.25	A/B	3-162	[»]
3SAI	X-ray	2.25	A/B	3-162	[»]
4ELB	X-ray	2.60	A/B/C/D/E/F/G/H	1-162	[»]
4ELE	X-ray	2.35	A/B/C/D/E/F/G/H	1-162	[»]
4ELF	X-ray	2.30	A/B/C/D/E/F/G/H	1-162	[»]
4ELG	X-ray	2.10	A/B/C/D/E/F/G/H	1-162	[»]
4ELH	X-ray	2.10	A/B/C/D/E/F/G/H	1-162	[»]

SMR

Q81R22. Positions 1-162.

ModBase

Search...

Protein-protein interaction databases

STRING

198094.BA_2237.

Protocols and materials databases

DNASU

1085515.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblBacteria

AAP26114; AAP26114; BA_2237.
AAT31357; AAT31357; GBAA_2237.
AAT54397; AAT54397; BAS2083.

GeneID

1085515.
2814627.
2849969.

KEGG

ban:BA_2237.
bar:GBAA_2237.
bat:BAS2083.

Phylogenomic databases

KO

K00287.

OMA

QDEEGVI.

ProtClustDB

CLSK916541.

Enzyme and pathway databases

BioCyc

BANT260799:GJAJ-2151-MONOMER.
BANT261594:GJ7F-2226-MONOMER.

UniPathway

UPA00077.

Family and domain databases

Gene3D

3.40.430.10. 1 hit.

InterPro

IPR012259. DHFR.
IPR024072. DHFR-like_dom.
IPR017925. DHFR_CS.
IPR001796. DHFR_dom.
[Graphical view]

Pfam

PF00186. DHFR_1. 1 hit.
[Graphical view]

PIRSF

PIRSF000194. DHFR. 1 hit.

PRINTS

PR00070. DHFR.

SUPFAM

SSF53597. SSF53597. 1 hit.

PROSITE

PS00075. DHFR_1. 1 hit.
PS51330. DHFR_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChEMBL

CHEMBL5270.

EvolutionaryTrace

Q81R22.

Entry information

Entry name

Q81R22_BACAN

Accession

Primary (citable) accession number: Q81R22
Secondary accession number(s): E9R6R2 , E9R6R3, E9R6R4, Q68SA0, Q6HZ92, Q6KT86

Entry history

Integrated into UniProtKB/TrEMBL:	June 1, 2003
Last sequence update:	June 1, 2003
Last modified:	May 1, 2013
This is version 91 of the entry and version 1 of the sequence. [Complete history]

Entry status

Unreviewed (UniProtKB/TrEMBL)