1DLS

METHOTREXATE-RESISTANT VARIANTS OF HUMAN DIHYDROFOLATE REDUCTASE WITH SUBSTITUTION OF LEUCINE 22: KINETICS, CRYSTALLOGRAPHY AND POTENTIAL AS SELECTABLE MARKERS

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
Pharos: Disease Associations

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

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
A	d1dlsa_	Alpha and beta proteins (a/b)	Dihydrofolate reductase-like	Dihydrofolate reductase-like	Dihydrofolate reductases	Dihydrofolate reductases, eukaryotic type	human (Homo sapiens ) [TaxId: 9606 ],	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	8040487	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	e1dlsA1	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 nucleotide binding nucleoside phosphate binding ion binding purine nucleotide binding organic cyclic compound binding anion binding adenyl nucleotide binding heterocyclic compound binding NADPH binding NADP binding small molecule binding RNA binding nucleic acid binding binding nucleotide binding nucleoside phosphate binding ion binding purine nucleotide binding organic cyclic compound binding anion binding adenyl nucleotide binding heterocyclic compound binding NADPH binding NADP binding small molecule binding RNA binding nucleic acid binding mRNA binding amide binding organic acid binding modified amino acid binding vitamin binding folic acid binding carboxylic acid 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 translation regulator activity mRNA regulatory element binding translation repressor activity translation regulator activity, nucleic acid binding translation repressor activity sequence-specific mRNA binding	regulation of cellular process cellular biosynthetic process negative regulation of biological process negative regulation of cellular metabolic process regulation of primary metabolic process post-transcriptional regulation of gene expression negative regulation of translation negative regulation of cellular process protein metabolic process negative regulation of protein metabolic process negative regulation of macromolecule metabolic process regulation of biosynthetic process regulation of biological process cellular metabolic process regulation of cellular process cellular biosynthetic process negative regulation of biological process negative regulation of cellular metabolic process regulation of primary metabolic process post-transcriptional regulation of gene expression negative regulation of translation negative regulation of cellular process protein metabolic process negative regulation of protein metabolic process negative regulation of macromolecule metabolic process regulation of biosynthetic process regulation of biological process cellular metabolic process regulation of protein metabolic process negative regulation of metabolic process biological regulation regulation of cellular metabolic process primary metabolic process regulation of macromolecule metabolic process gene expression translation macromolecule biosynthetic process negative regulation of cellular biosynthetic process regulation of cellular biosynthetic process regulation of gene expression negative regulation of gene expression biosynthetic process negative regulation of biosynthetic process regulation of translation negative regulation of macromolecule biosynthetic process regulation of macromolecule biosynthetic process metabolic process cellular process macromolecule metabolic process regulation of 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 regulation of catalytic activity positive regulation of catalytic activity regulation of oxidoreductase activity positive regulation of oxidoreductase activity positive regulation of nitric-oxide synthase activity regulation of molecular function positive regulation of molecular function regulation of monooxygenase activity positive regulation of monooxygenase activity regulation of nitric-oxide synthase activity small molecule metabolic process one-carbon metabolic process folic acid-containing compound metabolic process tetrahydrofolate metabolic process pteridine-containing compound metabolic process cellular modified amino acid metabolic process oxoacid metabolic process dicarboxylic acid metabolic process dihydrofolate metabolic process carboxylic acid metabolic process organic acid metabolic process cellular response to stimulus cellular response to oxidative stress detoxification regulation of cellular response to stress reactive oxygen species metabolic process cellular response to chemical stress regulation of cellular response to oxidative stress response to superoxide cellular oxidant detoxification cellular response to oxygen radical cellular response to reactive oxygen species cellular response to stress response to stress regulation of response to stress regulation of response to oxidative stress cellular detoxification regulation of superoxide metabolic process cellular response to oxygen-containing compound response to reactive oxygen species regulation of removal of superoxide radicals response to toxic substance superoxide metabolic process removal of superoxide radicals response to oxidative stress cellular response to chemical stimulus regulation of response to stimulus regulation of response to reactive oxygen species cellular response to superoxide regulation of reactive oxygen species metabolic process cellular response to toxic substance response to oxygen radical vitamin metabolic process amide metabolic process water-soluble vitamin metabolic process folic acid metabolic process multicellular organismal process cellular developmental process cell projection organization cell development neuron projection development regeneration response to axon injury neuron projection regeneration cellular component organization neurogenesis multicellular organism development axon regeneration neuron differentiation cell differentiation anatomical structure development cellular component organization or biogenesis response to wounding system development developmental process plasma membrane bounded cell projection organization nervous system development axon development generation of neurons neuron development polyol metabolic process small molecule biosynthetic process organic hydroxy compound metabolic process alcohol metabolic process diol biosynthetic process diol metabolic process tetrahydrobiopterin biosynthetic process tetrahydrobiopterin metabolic process organic hydroxy compound biosynthetic process pteridine-containing compound biosynthetic process polyol biosynthetic process alcohol biosynthetic process folic acid-containing compound biosynthetic process cellular modified amino acid biosynthetic process tetrahydrofolate biosynthetic process	membrane-bounded organelle intracellular organelle intracellular anatomical structure mitochondrion organelle cytoplasm cellular anatomical entity intracellular membrane-bounded organelle 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

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	Pharos: P00374	pancytopenia rheumatoid arthritis megaloblastic anemia osteosarcoma breast carcinoma constitutional megaloblastic anemia with severe neurologic disease Neoplasm Metastasis inborn errors of metabolism psoriasis breast cancer colorectal cancer nervous system disorder non-small cell lung carcinoma female infertility mature T-cell and NK-cell non-Hodgkin lymphoma pancytopenia rheumatoid arthritis megaloblastic anemia osteosarcoma breast carcinoma constitutional megaloblastic anemia with severe neurologic disease Neoplasm Metastasis inborn errors of metabolism psoriasis breast cancer colorectal cancer nervous system disorder non-small cell lung carcinoma female infertility mature T-cell and NK-cell non-Hodgkin lymphoma endometriosis pancreatic intraductal papillary-mucinous carcinoma glioblastoma adrenal cortex carcinoma autism large cell medulloblastoma malaria tuberculosis malignant glioma malignant pleural mesothelioma congenital anemia medulloblastoma drug-induced liver injury pancreatic intraductal papillary-mucinous neoplasm intellectual disability psoriatic arthritis leukemia malignant colon neoplasm malignant mesothelioma colorectal carcinoma mycosis fungoides gestational trophoblastic neoplasm pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia acute lymphoblastic leukemia primitive neuroectodermal tumor atypical teratoid rhabdoid tumor juvenile idiopathic arthritis bone osteosarcoma lung cancer Burkitt lymphoma malignant ependymoma

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.