4ISK

Crystal structure of E.coli thymidylate synthase with dUMP and the BGC 945 inhibitor

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
Protein Modification Annotation

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

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
C	d4iskc1	Alpha and beta proteins (a+b)	Thymidylate synthase/dCMP hydroxymethylase	Thymidylate synthase/dCMP hydroxymethylase	Thymidylate synthase/dCMP hydroxymethylase	Thymidylate synthase	(Escherichia coli K-12 ) [TaxId: 83333 ],	SCOPe (2.08)
C	d4iskc2	Artifacts	Tags	Tags	Tags	N-terminal Tags	(Escherichia coli K-12 ) [TaxId: 83333 ],	SCOPe (2.08)
E	d4iske1	Alpha and beta proteins (a+b)	Thymidylate synthase/dCMP hydroxymethylase	Thymidylate synthase/dCMP hydroxymethylase	Thymidylate synthase/dCMP hydroxymethylase	Thymidylate synthase	(Escherichia coli K-12 ) [TaxId: 83333 ],	SCOPe (2.08)
E	d4iske2	Artifacts	Tags	Tags	Tags	N-terminal Tags	(Escherichia coli K-12 ) [TaxId: 83333 ],	SCOPe (2.08)
A	d4iska1	Alpha and beta proteins (a+b)	Thymidylate synthase/dCMP hydroxymethylase	Thymidylate synthase/dCMP hydroxymethylase	Thymidylate synthase/dCMP hydroxymethylase	Thymidylate synthase	(Escherichia coli K-12 ) [TaxId: 83333 ],	SCOPe (2.08)
A	d4iska2	Artifacts	Tags	Tags	Tags	N-terminal Tags	(Escherichia coli K-12 ) [TaxId: 83333 ],	SCOPe (2.08)
B	d4iskb1	Alpha and beta proteins (a+b)	Thymidylate synthase/dCMP hydroxymethylase	Thymidylate synthase/dCMP hydroxymethylase	Thymidylate synthase/dCMP hydroxymethylase	Thymidylate synthase	(Escherichia coli K-12 ) [TaxId: 83333 ],	SCOPe (2.08)
B	d4iskb2	Artifacts	Tags	Tags	Tags	N-terminal Tags	(Escherichia coli K-12 ) [TaxId: 83333 ],	SCOPe (2.08)
D	d4iskd1	Alpha and beta proteins (a+b)	Thymidylate synthase/dCMP hydroxymethylase	Thymidylate synthase/dCMP hydroxymethylase	Thymidylate synthase/dCMP hydroxymethylase	Thymidylate synthase	(Escherichia coli K-12 ) [TaxId: 83333 ],	SCOPe (2.08)
D	d4iskd2	Artifacts	Tags	Tags	Tags	N-terminal Tags	(Escherichia coli K-12 ) [TaxId: 83333 ],	SCOPe (2.08)
F	d4iskf1	Alpha and beta proteins (a+b)	Thymidylate synthase/dCMP hydroxymethylase	Thymidylate synthase/dCMP hydroxymethylase	Thymidylate synthase/dCMP hydroxymethylase	Thymidylate synthase	(Escherichia coli K-12 ) [TaxId: 83333 ],	SCOPe (2.08)
F	d4iskf2	Artifacts	Tags	Tags	Tags	N-terminal Tags	(Escherichia coli K-12 ) [TaxId: 83333 ],	SCOPe (2.08)
G	d4iskg1	Alpha and beta proteins (a+b)	Thymidylate synthase/dCMP hydroxymethylase	Thymidylate synthase/dCMP hydroxymethylase	Thymidylate synthase/dCMP hydroxymethylase	Thymidylate synthase	(Escherichia coli K-12 ) [TaxId: 83333 ],	SCOPe (2.08)
G	d4iskg2	Artifacts	Tags	Tags	Tags	N-terminal Tags	(Escherichia coli K-12 ) [TaxId: 83333 ],	SCOPe (2.08)
H	d4iskh1	Alpha and beta proteins (a+b)	Thymidylate synthase/dCMP hydroxymethylase	Thymidylate synthase/dCMP hydroxymethylase	Thymidylate synthase/dCMP hydroxymethylase	Thymidylate synthase	(Escherichia coli K-12 ) [TaxId: 83333 ],	SCOPe (2.08)
H	d4iskh2	Artifacts	Tags	Tags	Tags	N-terminal Tags	(Escherichia coli K-12 ) [TaxId: 83333 ],	SCOPe (2.08)

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
C	SCOP2B Superfamily	Thymidylate synthase/dCMP hydroxymethylase	8041736	3000544	SCOP2B (2022-06-29)
E	SCOP2B Superfamily	Thymidylate synthase/dCMP hydroxymethylase	8041736	3000544	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	Thymidylate synthase/dCMP hydroxymethylase	8041736	3000544	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	Thymidylate synthase/dCMP hydroxymethylase	8041736	3000544	SCOP2B (2022-06-29)
D	SCOP2B Superfamily	Thymidylate synthase/dCMP hydroxymethylase	8041736	3000544	SCOP2B (2022-06-29)
F	SCOP2B Superfamily	Thymidylate synthase/dCMP hydroxymethylase	8041736	3000544	SCOP2B (2022-06-29)
G	SCOP2B Superfamily	Thymidylate synthase/dCMP hydroxymethylase	8041736	3000544	SCOP2B (2022-06-29)
H	SCOP2B Superfamily	Thymidylate synthase/dCMP hydroxymethylase	8041736	3000544	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)
C	Thymidylat_synt	e4iskC1	A: a+b two layers	X: Thymidylate synthase/dCMP hydroxymethylase (From Topology)	H: Thymidylate synthase/dCMP hydroxymethylase (From Topology)	T: Thymidylate synthase/dCMP hydroxymethylase	F: Thymidylat_synt	ECOD (1.6)
E	Thymidylat_synt	e4iskE1	A: a+b two layers	X: Thymidylate synthase/dCMP hydroxymethylase (From Topology)	H: Thymidylate synthase/dCMP hydroxymethylase (From Topology)	T: Thymidylate synthase/dCMP hydroxymethylase	F: Thymidylat_synt	ECOD (1.6)
A	Thymidylat_synt	e4iskA1	A: a+b two layers	X: Thymidylate synthase/dCMP hydroxymethylase (From Topology)	H: Thymidylate synthase/dCMP hydroxymethylase (From Topology)	T: Thymidylate synthase/dCMP hydroxymethylase	F: Thymidylat_synt	ECOD (1.6)
B	Thymidylat_synt	e4iskB1	A: a+b two layers	X: Thymidylate synthase/dCMP hydroxymethylase (From Topology)	H: Thymidylate synthase/dCMP hydroxymethylase (From Topology)	T: Thymidylate synthase/dCMP hydroxymethylase	F: Thymidylat_synt	ECOD (1.6)
D	Thymidylat_synt	e4iskD1	A: a+b two layers	X: Thymidylate synthase/dCMP hydroxymethylase (From Topology)	H: Thymidylate synthase/dCMP hydroxymethylase (From Topology)	T: Thymidylate synthase/dCMP hydroxymethylase	F: Thymidylat_synt	ECOD (1.6)
F	Thymidylat_synt	e4iskF1	A: a+b two layers	X: Thymidylate synthase/dCMP hydroxymethylase (From Topology)	H: Thymidylate synthase/dCMP hydroxymethylase (From Topology)	T: Thymidylate synthase/dCMP hydroxymethylase	F: Thymidylat_synt	ECOD (1.6)
G	Thymidylat_synt	e4iskG1	A: a+b two layers	X: Thymidylate synthase/dCMP hydroxymethylase (From Topology)	H: Thymidylate synthase/dCMP hydroxymethylase (From Topology)	T: Thymidylate synthase/dCMP hydroxymethylase	F: Thymidylat_synt	ECOD (1.6)
H	Thymidylat_synt	e4iskH1	A: a+b two layers	X: Thymidylate synthase/dCMP hydroxymethylase (From Topology)	H: Thymidylate synthase/dCMP hydroxymethylase (From Topology)	T: Thymidylate synthase/dCMP hydroxymethylase	F: Thymidylat_synt	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
C	3.30.572.10	Alpha Beta	2-Layer Sandwich	Thymidylate Synthase	Chain A	CATH (4.3.0)
E	3.30.572.10	Alpha Beta	2-Layer Sandwich	Thymidylate Synthase	Chain A	CATH (4.3.0)
A	3.30.572.10	Alpha Beta	2-Layer Sandwich	Thymidylate Synthase	Chain A	CATH (4.3.0)
B	3.30.572.10	Alpha Beta	2-Layer Sandwich	Thymidylate Synthase	Chain A	CATH (4.3.0)
D	3.30.572.10	Alpha Beta	2-Layer Sandwich	Thymidylate Synthase	Chain A	CATH (4.3.0)
F	3.30.572.10	Alpha Beta	2-Layer Sandwich	Thymidylate Synthase	Chain A	CATH (4.3.0)
G	3.30.572.10	Alpha Beta	2-Layer Sandwich	Thymidylate Synthase	Chain A	CATH (4.3.0)
H	3.30.572.10	Alpha Beta	2-Layer Sandwich	Thymidylate Synthase	Chain A	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B, C, D, E A, B, C, D, E, F, G, H	PF00303	Thymidylate synthase (Thymidylat_synt)	Thymidylate synthase	This is a family of proteins that are flavin-dependent thymidylate synthases.	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B, C, D, E A, B, C, D, E, F, G, H	Thymidylate synthase	cation binding magnesium ion binding ion binding binding metal ion binding small molecule binding transferase activity, transferring one-carbon groups transferase activity methyltransferase activity thymidylate synthase activity 5,10-methylenetetrahydrofolate-dependent methyltransferase activity catalytic activity identical protein binding protein binding cation binding magnesium ion binding ion binding binding metal ion binding small molecule binding transferase activity, transferring one-carbon groups transferase activity methyltransferase activity thymidylate synthase activity 5,10-methylenetetrahydrofolate-dependent methyltransferase activity catalytic activity identical protein binding protein binding protein homodimerization activity protein dimerization activity RNA binding organic cyclic compound binding nucleic acid binding	pyrimidine deoxyribonucleotide metabolic process deoxyribose phosphate biosynthetic process nucleotide biosynthetic process carbohydrate derivative metabolic process pyrimidine nucleotide metabolic process pyrimidine deoxyribonucleoside monophosphate metabolic process nucleobase-containing compound metabolic process deoxyribonucleotide biosynthetic process deoxyribonucleotide metabolic process pyrimidine deoxyribonucleotide biosynthetic process nucleobase-containing small molecule metabolic process dTMP metabolic process phosphate-containing compound metabolic process deoxyribonucleoside monophosphate biosynthetic process pyrimidine deoxyribonucleotide metabolic process deoxyribose phosphate biosynthetic process nucleotide biosynthetic process carbohydrate derivative metabolic process pyrimidine nucleotide metabolic process pyrimidine deoxyribonucleoside monophosphate metabolic process nucleobase-containing compound metabolic process deoxyribonucleotide biosynthetic process deoxyribonucleotide metabolic process pyrimidine deoxyribonucleotide biosynthetic process nucleobase-containing small molecule metabolic process dTMP metabolic process phosphate-containing compound metabolic process deoxyribonucleoside monophosphate biosynthetic process dTMP biosynthetic process small molecule metabolic process pyrimidine deoxyribonucleoside monophosphate biosynthetic process pyrimidine-containing compound biosynthetic process nucleoside monophosphate metabolic process phosphorus metabolic process nucleoside phosphate metabolic process carbohydrate derivative biosynthetic process pyrimidine nucleoside monophosphate metabolic process pyrimidine-containing compound metabolic process cellular metabolic process 2'-deoxyribonucleotide metabolic process 2'-deoxyribonucleotide biosynthetic process primary metabolic process nucleotide metabolic process deoxyribose phosphate metabolic process nucleobase-containing compound biosynthetic process deoxyribonucleoside monophosphate metabolic process nucleoside monophosphate biosynthetic process biosynthetic process organophosphate metabolic process organophosphate biosynthetic process nucleoside phosphate biosynthetic process metabolic process cellular process pyrimidine nucleoside monophosphate biosynthetic process pyrimidine nucleotide biosynthetic process methylation response to stimulus response to radiation response to abiotic stimulus regulation of cellular process cellular biosynthetic process regulation of primary metabolic process post-transcriptional regulation of gene expression protein metabolic process regulation of biosynthetic process regulation of biological process regulation of protein metabolic process biological regulation regulation of cellular metabolic process regulation of macromolecule metabolic process gene expression translation macromolecule biosynthetic process regulation of cellular biosynthetic process regulation of gene expression regulation of translation regulation of macromolecule biosynthetic process macromolecule metabolic process regulation of metabolic process pyrimidine deoxyribonucleoside triphosphate biosynthetic process dTTP biosynthetic process pyrimidine deoxyribonucleoside triphosphate metabolic process pyrimidine nucleoside triphosphate biosynthetic process pyrimidine nucleoside triphosphate metabolic process dTTP metabolic process nucleoside triphosphate biosynthetic process nucleoside triphosphate metabolic process	intracellular anatomical structure cytoplasm cellular anatomical entity cytosol

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B, C, D, E A, B, C, D, E, F, G, H	IPR036926	Thymidylate synthase/dCMP hydroxymethylase superfamily	Homologous Superfamily
A, B, C, D, E A, B, C, D, E, F, G, H	IPR000398	Thymidylate synthase	Family
A, B, C, D, E A, B, C, D, E, F, G, H	IPR045097	Thymidylate synthase/dCMP hydroxymethylase	Family
A, B, C, D, E A, B, C, D, E, F, G, H	IPR020940	Thymidylate synthase, active site	Active Site
A, B, C, D, E A, B, C, D, E, F, G, H	IPR023451	Thymidylate synthase/dCMP hydroxymethylase domain	Domain

Protein Modification Annotation

Modified Residue(s)
Chain	Residue(s)	Description
A, B, C, D, E A, B, C, D, E, F, G, H	CXM	Parent Component: MET RESID: AA0363 , AA0493 PSI-MOD : N-carboxy-L-methionine MOD:00368 , N-(dihydroxymethyl)-L-methionine (fMet) MOD:01446 , N-(dihydroxymethyl)-L-methionine (Met) MOD:01447

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.