Summary Structural details Experimental details Functional details Sequence Neighbor History Downloads

3HBB

Structures of dihydrofolate reductase-thymidylate synthase of Trypanosoma cruzi in the folate-free state and in complex with two antifolate drugs, trimetrexate and methotrexate

Functional Information from GO Data

Chain	GOid	namespace	contents
A	0003824	molecular_function	catalytic activity
A	0004146	molecular_function	dihydrofolate reductase activity
A	0004799	molecular_function	thymidylate synthase activity
A	0005739	cellular_component	mitochondrion
A	0005829	cellular_component	cytosol
A	0006231	biological_process	dTMP biosynthetic process
A	0006730	biological_process	one-carbon metabolic process
A	0008168	molecular_function	methyltransferase activity
A	0009165	biological_process	nucleotide biosynthetic process
A	0016491	molecular_function	oxidoreductase activity
A	0016740	molecular_function	transferase activity
A	0016741	molecular_function	transferase activity, transferring one-carbon groups
A	0032259	biological_process	methylation
A	0046654	biological_process	tetrahydrofolate biosynthetic process
B	0003824	molecular_function	catalytic activity
B	0004146	molecular_function	dihydrofolate reductase activity
B	0004799	molecular_function	thymidylate synthase activity
B	0005739	cellular_component	mitochondrion
B	0005829	cellular_component	cytosol
B	0006231	biological_process	dTMP biosynthetic process
B	0006730	biological_process	one-carbon metabolic process
B	0008168	molecular_function	methyltransferase activity
B	0009165	biological_process	nucleotide biosynthetic process
B	0016491	molecular_function	oxidoreductase activity
B	0016740	molecular_function	transferase activity
B	0016741	molecular_function	transferase activity, transferring one-carbon groups
B	0032259	biological_process	methylation
B	0046654	biological_process	tetrahydrofolate biosynthetic process
C	0003824	molecular_function	catalytic activity
C	0004146	molecular_function	dihydrofolate reductase activity
C	0004799	molecular_function	thymidylate synthase activity
C	0005739	cellular_component	mitochondrion
C	0005829	cellular_component	cytosol
C	0006231	biological_process	dTMP biosynthetic process
C	0006730	biological_process	one-carbon metabolic process
C	0008168	molecular_function	methyltransferase activity
C	0009165	biological_process	nucleotide biosynthetic process
C	0016491	molecular_function	oxidoreductase activity
C	0016740	molecular_function	transferase activity
C	0016741	molecular_function	transferase activity, transferring one-carbon groups
C	0032259	biological_process	methylation
C	0046654	biological_process	tetrahydrofolate biosynthetic process
D	0003824	molecular_function	catalytic activity
D	0004146	molecular_function	dihydrofolate reductase activity
D	0004799	molecular_function	thymidylate synthase activity
D	0005739	cellular_component	mitochondrion
D	0005829	cellular_component	cytosol
D	0006231	biological_process	dTMP biosynthetic process
D	0006730	biological_process	one-carbon metabolic process
D	0008168	molecular_function	methyltransferase activity
D	0009165	biological_process	nucleotide biosynthetic process
D	0016491	molecular_function	oxidoreductase activity
D	0016740	molecular_function	transferase activity
D	0016741	molecular_function	transferase activity, transferring one-carbon groups
D	0032259	biological_process	methylation
D	0046654	biological_process	tetrahydrofolate biosynthetic process

Functional Information from PDB Data

site_id	AC1
Number of Residues	23
Details	BINDING SITE FOR RESIDUE NAP A 601

Chain	Residue
A	VAL27
A	LYS79
A	THR80
A	LEU99
A	SER100
A	SER101
A	THR102
A	GLY130
A	GLY131
A	ILE154
A	GLY156
A	ALA28
A	GLY157
A	SER158
A	TYR160
A	TMQ611
A	ILE35
A	GLY38
A	ARG39
A	SER40
A	ILE41
A	GLY77
A	ARG78

site_id	AC2
Number of Residues	12
Details	BINDING SITE FOR RESIDUE TMQ A 611

Chain	Residue
A	VAL26
A	VAL27
A	ALA28
A	ILE41
A	ASP48
A	MET49
A	PHE52
A	ILE84
A	PRO85
A	LEU91
A	ILE154
A	NAP601

site_id	AC3
Number of Residues	4
Details	BINDING SITE FOR RESIDUE SO4 A 701

Chain	Residue
A	ARG383
A	ARG384
D	ARG423
D	SER424

site_id	AC4
Number of Residues	3
Details	BINDING SITE FOR RESIDUE SO4 A 805

Chain	Residue
A	ARG39
A	ARG78
A	LYS79

site_id	AC5
Number of Residues	5
Details	BINDING SITE FOR RESIDUE SO4 A 813

Chain	Residue
A	ARG249
A	GLU250
B	TRP206
B	ARG208
B	LEU230

site_id	AC6
Number of Residues	3
Details	BINDING SITE FOR RESIDUE SO4 A 814

Chain	Residue
A	ARG323
A	GLU335
A	GLU336

site_id	AC7
Number of Residues	2
Details	BINDING SITE FOR RESIDUE SO4 A 815

Chain	Residue
A	PHE288
A	ARG290

site_id	AC8
Number of Residues	2
Details	BINDING SITE FOR RESIDUE SO4 A 817

Chain	Residue
A	ARG233
A	ARG235

site_id	AC9
Number of Residues	2
Details	BINDING SITE FOR RESIDUE EDO A 902

Chain	Residue
A	TRP206
B	EDO906

site_id	BC1
Number of Residues	4
Details	BINDING SITE FOR RESIDUE EDO A 904

Chain	Residue
A	SER212
A	TYR226
B	VAL253
B	SER467

site_id	BC2
Number of Residues	23
Details	BINDING SITE FOR RESIDUE NAP B 602

Chain	Residue
B	ALA28
B	ILE35
B	ARG39
B	SER40
B	ILE41
B	GLY77
B	ARG78
B	LYS79
B	THR80
B	LEU99
B	SER100
B	SER101
B	THR102
B	GLY130
B	GLY131
B	ILE154
B	GLY155
B	GLY156
B	GLY157
B	SER158
B	VAL159
B	TYR160
B	TMQ612

site_id	BC3
Number of Residues	7
Details	BINDING SITE FOR RESIDUE TMQ B 612

Chain	Residue
B	ASP48
B	PHE52
B	SER83
B	ILE154
B	HOH549
B	HOH558
B	NAP602

site_id	BC4
Number of Residues	3
Details	BINDING SITE FOR RESIDUE SO4 B 806

Chain	Residue
B	ARG323
B	GLU335
B	GLU336

site_id	BC5
Number of Residues	4
Details	BINDING SITE FOR RESIDUE SO4 B 809

Chain	Residue
B	ARG491
B	ARG493
B	GLU494
B	ASP498

site_id	BC6
Number of Residues	2
Details	BINDING SITE FOR RESIDUE SO4 B 818

Chain	Residue
B	GLN364
B	GLY365

site_id	BC7
Number of Residues	2
Details	BINDING SITE FOR RESIDUE SO4 B 821

Chain	Residue
B	ARG233
B	ARG235

site_id	BC8
Number of Residues	2
Details	BINDING SITE FOR RESIDUE SO4 B 823

Chain	Residue
B	PHE288
B	ARG290

site_id	BC9
Number of Residues	5
Details	BINDING SITE FOR RESIDUE EDO B 906

Chain	Residue
A	ARG177
A	EDO902
B	ASN252
B	VAL253
C	ASN413

site_id	CC1
Number of Residues	5
Details	BINDING SITE FOR RESIDUE SO4 C 702

Chain	Residue
B	ARG383
B	ARG384
C	ARG257
C	ARG423
C	SER424

site_id	CC2
Number of Residues	23
Details	BINDING SITE FOR RESIDUE NAP C 603

Chain	Residue
C	ALA28
C	ILE35
C	GLY38
C	ARG39
C	SER40
C	ILE41
C	GLY77
C	ARG78
C	LYS79
C	THR80
C	LEU99
C	SER100
C	SER101
C	THR102
C	GLY130
C	GLY131
C	ILE154
C	GLY156
C	GLY157
C	SER158
C	VAL159
C	TYR160
C	TMQ613

site_id	CC3
Number of Residues	10
Details	BINDING SITE FOR RESIDUE TMQ C 613

Chain	Residue
C	VAL26
C	VAL27
C	ASP48
C	MET49
C	PHE52
C	SER83
C	ILE84
C	PRO85
C	ILE154
C	NAP603

site_id	CC4
Number of Residues	5
Details	BINDING SITE FOR RESIDUE SO4 C 703

Chain	Residue
B	ARG257
B	ARG423
C	ARG383
C	ARG384
C	HOH565

site_id	CC5
Number of Residues	2
Details	BINDING SITE FOR RESIDUE SO4 C 802

Chain	Residue
C	ARG60
C	EDO908

site_id	CC6
Number of Residues	3
Details	BINDING SITE FOR RESIDUE SO4 C 807

Chain	Residue
C	ARG39
C	ARG78
C	LYS79

site_id	CC7
Number of Residues	7
Details	BINDING SITE FOR RESIDUE SO4 C 808

Chain	Residue
B	GLY351
B	ASN391
B	SER393
C	PHE350
C	GLY351
C	ASN391
C	SER393

site_id	CC8
Number of Residues	3
Details	BINDING SITE FOR RESIDUE SO4 C 812

Chain	Residue
C	PHE288
C	ARG290
C	EDO909

site_id	CC9
Number of Residues	2
Details	BINDING SITE FOR RESIDUE SO4 C 816

Chain	Residue
C	ARG233
C	ARG235

site_id	DC1
Number of Residues	4
Details	BINDING SITE FOR RESIDUE SO4 C 822

Chain	Residue
C	ARG491
C	ARG493
C	GLU494
C	ASP498

site_id	DC2
Number of Residues	3
Details	BINDING SITE FOR RESIDUE SO4 C 824

Chain	Residue
C	ARG323
C	GLU335
C	GLU336

site_id	DC3
Number of Residues	4
Details	BINDING SITE FOR RESIDUE EDO C 908

Chain	Residue
C	ARG286
C	VAL506
C	TYR509
C	SO4802

site_id	DC4
Number of Residues	4
Details	BINDING SITE FOR RESIDUE EDO C 909

Chain	Residue
C	VAL287
C	PHE288
C	HOH569
C	SO4812

site_id	DC5
Number of Residues	4
Details	BINDING SITE FOR RESIDUE EDO C 910

Chain	Residue
C	GLN173
C	ALA174
C	LYS229
C	ILE231

site_id	DC6
Number of Residues	7
Details	BINDING SITE FOR RESIDUE EDO C 912

Chain	Residue
B	ASN413
C	ASN252
C	VAL253
D	ARG177
D	ARG208
D	HOH552
D	EDO911

site_id	DC7
Number of Residues	24
Details	BINDING SITE FOR RESIDUE NAP D 604

Chain	Residue
D	ALA28
D	ILE35
D	GLY38
D	ARG39
D	SER40
D	ILE41
D	GLY77
D	ARG78
D	LYS79
D	THR80
D	LEU99
D	SER100
D	SER101
D	THR102
D	GLY130
D	GLY131
D	ILE154
D	GLY155
D	GLY156
D	GLY157
D	SER158
D	VAL159
D	TYR160
D	TMQ614

site_id	DC8
Number of Residues	9
Details	BINDING SITE FOR RESIDUE TMQ D 614

Chain	Residue
D	VAL26
D	VAL27
D	ALA28
D	ASP48
D	MET49
D	PHE52
D	PRO85
D	ILE154
D	NAP604

site_id	DC9
Number of Residues	5
Details	BINDING SITE FOR RESIDUE SO4 D 704

Chain	Residue
A	ARG257
A	ARG423
A	SER424
D	ARG383
D	ARG384

site_id	EC1
Number of Residues	2
Details	BINDING SITE FOR RESIDUE SO4 D 801

Chain	Residue
D	ARG60
D	TYR509

site_id	EC2
Number of Residues	2
Details	BINDING SITE FOR RESIDUE SO4 D 803

Chain	Residue
D	PHE288
D	ARG290

site_id	EC3
Number of Residues	2
Details	BINDING SITE FOR RESIDUE SO4 D 804

Chain	Residue
D	ARG482
D	PRO513

site_id	EC4
Number of Residues	2
Details	BINDING SITE FOR RESIDUE SO4 D 810

Chain	Residue
D	ARG491
D	ARG493

site_id	EC5
Number of Residues	3
Details	BINDING SITE FOR RESIDUE SO4 D 811

Chain	Residue
D	ARG323
D	GLU335
D	GLU336

site_id	EC6
Number of Residues	1
Details	BINDING SITE FOR RESIDUE SO4 D 819

Chain	Residue
D	ARG78

site_id	EC7
Number of Residues	2
Details	BINDING SITE FOR RESIDUE SO4 D 820

Chain	Residue
D	ARG233
D	ARG235

site_id	EC8
Number of Residues	5
Details	BINDING SITE FOR RESIDUE EDO D 901

Chain	Residue
C	SER467
D	ILE211
D	SER212
D	GLU214
D	TYR226

site_id	EC9
Number of Residues	7
Details	BINDING SITE FOR RESIDUE EDO D 903

Chain	Residue
C	ARG177
C	TRP206
C	ARG208
D	ARG249
D	GLU250
D	GLY251
D	EDO905

site_id	FC1
Number of Residues	5
Details	BINDING SITE FOR RESIDUE EDO D 905

Chain	Residue
C	ARG177
C	ARG208
D	ASN252
D	VAL253
D	EDO903

site_id	FC2
Number of Residues	6
Details	BINDING SITE FOR RESIDUE EDO D 907

Chain	Residue
C	ILE211
C	SER212
C	GLU214
D	HIS255
D	GLY261
D	SER467

site_id	FC3
Number of Residues	4
Details	BINDING SITE FOR RESIDUE EDO D 911

Chain	Residue
C	ARG249
C	EDO912
D	TRP206
D	ARG208

Functional Information from PROSITE/UniProt

site_id	PS00075
Number of Residues	23
Details	DHFR_1 Dihydrofolate reductase (DHFR) domain signature. GIGdgrsIPWnvpe.DmkfFrdvT

Chain	Residue	Details
A	GLY34-THR56

site_id	PS00091
Number of Residues	29
Details	THYMIDYLATE_SYNTHASE Thymidylate synthase active site. RrmLftaWNpsalprma.....LpPCHllaQFyV

Chain	Residue	Details
A	ARG383-VAL411

Functional Information from SwissProt/UniProt

site_id	SWS_FT_FI2
Number of Residues	128
Details	Binding site: {}

Chain

Residue

Details

Catalytic Information from CSA

site_id	CSA1
Number of Residues	3
Details	Annotated By Reference To The Literature 1b02

Chain	Residue	Details
A	CYS403
A	ASN434
A	SER437

site_id	CSA2
Number of Residues	3
Details	Annotated By Reference To The Literature 1b02

Chain	Residue	Details
B	CYS403
B	ASN434
B	SER437

site_id	CSA3
Number of Residues	3
Details	Annotated By Reference To The Literature 1b02

Chain	Residue	Details
C	CYS403
C	ASN434
C	SER437

site_id	CSA4
Number of Residues	3
Details	Annotated By Reference To The Literature 1b02

Chain	Residue	Details
D	CYS403
D	ASN434
D	SER437

site_id	CSA5
Number of Residues	2
Details	Annotated By Reference To The Literature 1b02

Chain	Residue	Details
A	ASP48
A	ILE41

site_id	CSA6
Number of Residues	2
Details	Annotated By Reference To The Literature 1b02

Chain	Residue	Details
B	ASP48
B	ILE41

site_id	CSA7
Number of Residues	2
Details	Annotated By Reference To The Literature 1b02

Chain	Residue	Details
C	ASP48
C	ILE41

site_id	CSA8
Number of Residues	2
Details	Annotated By Reference To The Literature 1b02

Chain	Residue	Details
D	ASP48
D	ILE41

site_id	CSA9
Number of Residues	6
Details	Annotated By Reference To The Literature 1b02

Chain	Residue	Details
A	ASP426
A	ASP462
A	CYS403
A	HIS464
A	SER424
A	GLU295

site_id	CSA10
Number of Residues	6
Details	Annotated By Reference To The Literature 1b02

Chain	Residue	Details
B	ASP426
B	ASP462
B	CYS403
B	HIS464
B	SER424
B	GLU295

site_id	CSA11
Number of Residues	6
Details	Annotated By Reference To The Literature 1b02

Chain	Residue	Details
C	ASP426
C	ASP462
C	CYS403
C	HIS464
C	SER424
C	GLU295

site_id	CSA12
Number of Residues	6
Details	Annotated By Reference To The Literature 1b02

Chain	Residue	Details
D	ASP426
D	ASP462
D	CYS403
D	HIS464
D	SER424
D	GLU295

		Sequence (fasta)
		PDBx/mmCIF
		PDBML format (no-atom)
		PDB format (full)
		Validation report (PDF)
		EDMap 2fo-fc (MTZ)