3DFR

CRYSTAL STRUCTURES OF ESCHERICHIA COLI AND LACTOBACILLUS CASEI DIHYDROFOLATE REDUCTASE REFINED AT 1.7 ANGSTROMS RESOLUTION. I. GENERAL FEATURES AND BINDING OF METHOTREXATE

External Resource: Annotation

Domain Annotation: SCOP/SCOPe Classification
Domain Annotation: SCOP2 Classification
Domain Annotation: ECOD Classification
Domain Annotation: CATH
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Structure Motif: Primary M-CSA Annotation

Domain Annotation: SCOP/SCOPe Classification SCOP-e Database Homepage

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
A	d3dfra_	Alpha and beta proteins (a/b)	Dihydrofolate reductase-like	Dihydrofolate reductase-like	Dihydrofolate reductases	Dihydrofolate reductase, prokaryotic type	(Lacticaseibacillus casei ) [TaxId: 1582 ],	SCOPe (2.08)

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
A	SCOP2B Superfamily	Dihydrofolate reductase-like	8032717	3001255	SCOP2B (2022-06-29)

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A	DHFR_1	e3dfrA1	A: a/b three-layered sandwiches	X: Dihydrofolate reductases (From Topology)	H: Dihydrofolate reductases (From Topology)	T: Dihydrofolate reductases	F: DHFR_1	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	3.40.430.10	Alpha Beta	3-Layer(aba) Sandwich	Dihydrofolate Reductase, subunit A	Dihydrofolate Reductase, subunit A	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	PF00186	Dihydrofolate reductase (DHFR_1)	Dihydrofolate reductase	-	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	DIHYDROFOLATE REDUCTASE	binding nucleoside phosphate binding purine nucleotide binding organic cyclic compound binding adenyl nucleotide binding nucleotide binding heterocyclic compound binding NADP binding small molecule binding dihydrofolate reductase activity oxidoreductase activity oxidoreductase activity, acting on the CH-NH group of donors, NAD or NADP as acceptor oxidoreductase activity, acting on the CH-NH group of donors catalytic activity	response to methotrexate response to stimulus response to chemical response to oxygen-containing compound response to nitrogen compound response to organic cyclic compound small molecule metabolic process metabolic process cellular process one-carbon metabolic process oxoacid metabolic process dicarboxylic acid metabolic process dihydrofolate metabolic process carboxylic acid metabolic process response to methotrexate response to stimulus response to chemical response to oxygen-containing compound response to nitrogen compound response to organic cyclic compound small molecule metabolic process metabolic process cellular process one-carbon metabolic process oxoacid metabolic process dicarboxylic acid metabolic process dihydrofolate metabolic process carboxylic acid metabolic process modified amino acid metabolic process organic acid metabolic process folic acid-containing compound metabolic process pteridine-containing compound metabolic process vitamin metabolic process amide metabolic process water-soluble vitamin metabolic process folic acid metabolic process response to antibiotic folic acid-containing compound biosynthetic process modified amino acid biosynthetic process biosynthetic process pteridine-containing compound biosynthetic process tetrahydrofolate biosynthetic process tetrahydrofolate metabolic process	cellular anatomical structure intracellular anatomical structure cytoplasm cytosol

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR017925	Dihydrofolate reductase conserved site	Conserved Site
A	IPR012259	Dihydrofolate reductase	Family
A	IPR024072	Dihydrofolate reductase-like domain superfamily	Homologous Superfamily
A	IPR001796	Dihydrofolate reductase domain	Domain

Structure Motif Annotation: Mechanism and Catalytic Site Atlas M-CSA Database Homepage

Chains	Enzyme Name	Description	Catalytic Residues
A	dihydrofolate reductase (bacterial) M-CSA #112	Dihydrofolate reductase catalyses the reduction of 7,8-dihydrofolate (DHF) to 5,6,7,8-tetrahydrofolate (THF) by stereospecific hydride transfer from a NADPH cofactor to the C6 atom of the pterin ring with concomitant protonation at N(5). DHFR plays a central role cell maintenance of THF reserves, which are essential for purine and thimidylate synthesis and hence for cell growth and proliferation. As DHFR is the sole source of THF, the enzyme is the Achilles heel of rapidly proliferating cells and, therefore, has been a major focus in the development of anticancer and antibacterial reagents. Much interest has been generated in this enzyme due to its potential as a target for antibacterial and anticancer drugs. It is ubiquitous throughout evolution, but always most important in cells which are dividing rapidly, hence its value as a drug target against infections and cancer.	Defined by 9 residues: LEU:A-4LEU:A-19TRP:A-21ASP:A-26LEU:A-27PHE:A-30LEU:A-54LEU:A-94THR:A-116 \| Explore in 3D: M-CSA Motif Definition Search M-CSA Motif EC: 1.5.1.3 (PDB Primary Data) Search M-CSA Motif + EC 1.5.1.3

RCSB PDB Core Operations are funded by the U.S. National Science Foundation (DBI-2321666), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM157729.