Structure of PDB 6pf3 Chain A Binding Site BS02

Receptor Information

>6pf3 Chain A (length=285) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]

SELQYLGQIQHILRCGVRKDDRTGTGTLSVFGMQARYSLRDEFPLLTTKR
VFWKGVLEELLWFIKGSTNAKELSSKGVKIWDANGSRDFLDSLGFSTREE
GDLGPVYGFQWRHFGAEYRDMESDYSGQGVDQLQRVIDTIKTNPDDRRII
MCAWNPRDLPLMALPPCHALCQFYVVNSELSCQLYQRSGDMGLGVPFNIA
SYALLTYMIAHITGLKPGDFIHTLGDAHIYLNHIEPLKIQLQREPRPFPK
LRILRKVEKIDDFKAEDFQIEGYNPHPTIKMEMAV

Ligand information

Ligand ID

OE7

InChI

InChI=1S/C21H16ClN5O4/c22-13-5-6-14(20(30)31)15(8-13)25-18(28)11-3-1-10(2-4-11)7-12-9-24-17-16(12)19(29)27-21(23)26-17/h1-6,8-9H,7H2,(H,25,28)(H,30,31)(H4,23,24,26,27,29)

InChIKey

OBHYLCXTIVOOGV-UHFFFAOYSA-N

SMILES

Software	SMILES
ACDLabs 12.01	N=2c1ncc(c1C(=O)NC=2N)Cc3ccc(cc3)C(=O)Nc4cc(Cl)ccc4C(O)=O
CACTVS 3.385	NC1=Nc2[nH]cc(Cc3ccc(cc3)C(=O)Nc4cc(Cl)ccc4C(O)=O)c2C(=O)N1
OpenEye OEToolkits 2.0.7	c1cc(ccc1Cc2c[nH]c3c2C(=O)NC(=N3)N)C(=O)Nc4cc(ccc4C(=O)O)Cl

Formula

C21 H16 Cl N5 O4

Name

2-({4-[(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)methyl]benzene-1-carbonyl}amino)-4-chlorobenzoic acid

PDB chain

6pf3 Chain A Residue 601 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]

Receptor-Ligand Complex Structure

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Structure summary

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PDB	6pf3 Structure activity relationship towards design of cryptosporidium specific thymidylate synthase inhibitors.
Resolution	2.391 Å
Binding residue (original residue number in PDB)	F80 I108 D218 L221 G222 F225 Y258 M311 A312
Binding residue (residue number reindexed from 1)	F52 I80 D190 L193 G194 F197 Y230 M283 A284
Annotation score	1
Binding affinity	PDBbind-CN: -logKd/Ki=4.55,IC50=28uM

Enzymatic activity

Catalytic site (original residue number in PDB)	E87 W109 Y135 C195 R215 D218
Catalytic site (residue number reindexed from 1)	E59 W81 Y107 C167 R187 D190
Enzyme Commision number	2.1.1.45: thymidylate synthase.

Gene Ontology

	Molecular Function
GO:0000900	mRNA regulatory element binding translation repressor activity
GO:0003729	mRNA binding
GO:0004799	thymidylate synthase activity
GO:0005542	folic acid binding
GO:0008168	methyltransferase activity
GO:0016741	transferase activity, transferring one-carbon groups
GO:0042803	protein homodimerization activity
GO:1901363	heterocyclic compound binding
GO:1990825	sequence-specific mRNA binding

	Biological Process
GO:0006206	pyrimidine nucleobase metabolic process
GO:0006231	dTMP biosynthetic process
GO:0006235	dTTP biosynthetic process
GO:0006417	regulation of translation
GO:0007623	circadian rhythm
GO:0009165	nucleotide biosynthetic process
GO:0009410	response to xenobiotic stimulus
GO:0009636	response to toxic substance
GO:0014070	response to organic cyclic compound
GO:0017148	negative regulation of translation
GO:0019860	uracil metabolic process
GO:0032259	methylation
GO:0032570	response to progesterone
GO:0033189	response to vitamin A
GO:0034097	response to cytokine
GO:0035999	tetrahydrofolate interconversion
GO:0045471	response to ethanol
GO:0046653	tetrahydrofolate metabolic process
GO:0046683	response to organophosphorus
GO:0048589	developmental growth
GO:0051216	cartilage development
GO:0051384	response to glucocorticoid
GO:0051593	response to folic acid
GO:0060574	intestinal epithelial cell maturation
GO:0071897	DNA biosynthetic process
GO:0097421	liver regeneration

	Cellular Component
GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005739	mitochondrion
GO:0005743	mitochondrial inner membrane
GO:0005759	mitochondrial matrix
GO:0005829	cytosol

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Molecular Function

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Cellular Component

External links

PDB	RCSB:6pf3, PDBe:6pf3, PDBj:6pf3
PDBsum	6pf3
PubMed	31536894
UniProt	P04818\|TYSY_HUMAN Thymidylate synthase (Gene Name=TYMS)

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