2CNG

Structural Insights into the Design of Nonpeptidic Isothiazolidinone- Containing Inhibitors of Protein Tyrosine Phosphatase 1B

Functional Information from GO Data

Chain	GOid	namespace	contents
A	0004725	molecular_function	protein tyrosine phosphatase activity
A	0006470	biological_process	protein dephosphorylation
A	0016311	biological_process	dephosphorylation

Functional Information from PDB Data

site_id	AC1
Number of Residues	6
Details	BINDING SITE FOR RESIDUE MG A1300

Chain	Residue
A	HOH2062
A	HOH2063
A	HOH2075
A	HOH2076
A	HOH2158
A	HOH2159

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site_id	AC2
Number of Residues	23
Details	BINDING SITE FOR RESIDUE IZE A1299

Chain	Residue
A	VAL49
A	ASP181
A	PHE182
A	CYS215
A	SER216
A	ALA217
A	ILE219
A	GLY220
A	ARG221
A	ASP236
A	LYS239
A	PRO241
A	GLN262
A	GLN266
A	ILE281
A	MET282
A	GOL1302
A	HOH2064
A	HOH2065
A	HOH2250
A	TYR46
A	ARG47
A	ASP48

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site_id	AC3
Number of Residues	6
Details	BINDING SITE FOR RESIDUE GOL A1301

Chain	Residue
A	PRO89
A	CYS92
A	PHE135
A	HOH2252
A	HOH2253
A	HOH2254

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site_id	AC4
Number of Residues	4
Details	BINDING SITE FOR RESIDUE GOL A1302

Chain	Residue
A	ASP48
A	GLY259
A	GLN262
A	IZE1299

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Functional Information from PROSITE/UniProt

site_id	PS00383
Number of Residues	11
Details	TYR_PHOSPHATASE_1 Tyrosine specific protein phosphatases active site. VHCsaGigRSG

Chain	Residue	Details
A	VAL213-GLY223

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Functional Information from SwissProt/UniProt

site_id	SWS_FT_FI1
Number of Residues	274
Details	Domain: {"description":"Tyrosine-protein phosphatase","evidences":[{"source":"PROSITE-ProRule","id":"PRU00160","evidenceCode":"ECO:0000255"}]}

Chain

Residue

Details

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site_id	SWS_FT_FI2
Number of Residues	1
Details	Active site: {"description":"Phosphocysteine intermediate"}

Chain

Residue

Details

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site_id	SWS_FT_FI3
Number of Residues	1
Details	Binding site: {}

Chain

Residue

Details

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site_id	SWS_FT_FI4
Number of Residues	7
Details	Binding site: {"evidences":[{"evidenceCode":"ECO:0000250"}]}

Chain

Residue

Details

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site_id	SWS_FT_FI5
Number of Residues	1
Details	Modified residue: {"description":"Phosphotyrosine","evidences":[{"source":"PubMed","id":"15592455","evidenceCode":"ECO:0007744"}]}

Chain

Residue

Details

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site_id	SWS_FT_FI6
Number of Residues	1
Details	Modified residue: {"description":"Phosphoserine; by PKB/AKT1, CLK1 and CLK2","evidences":[{"source":"PubMed","id":"10480872","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"11579209","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"23186163","evidenceCode":"ECO:0007744"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI7
Number of Residues	1
Details	Modified residue: {"description":"Phosphotyrosine; by EGFR","evidences":[{"source":"PubMed","id":"9355745","evidenceCode":"ECO:0000269"}]}

Chain

Residue

Details

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site_id	SWS_FT_FI8
Number of Residues	1
Details	Modified residue: {"description":"S-nitrosocysteine; in reversibly inhibited form","evidences":[{"source":"PubMed","id":"22169477","evidenceCode":"ECO:0000269"}]}

Chain

Residue

Details

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site_id	SWS_FT_FI9
Number of Residues	2
Details	Modified residue: {"description":"Phosphoserine; by CLK1 and CLK2","evidences":[{"source":"PubMed","id":"10480872","evidenceCode":"ECO:0000269"}]}

Chain

Residue

Details

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site_id	SWS_FT_FI10
Number of Residues	2
Details	Cross-link: {"description":"N,N-(cysteine-1,S-diyl)serine (Cys-Ser); in inhibited form","evidences":[{"source":"PubMed","id":"12802338","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"12802339","evidenceCode":"ECO:0000269"}]}

Chain

Residue

Details

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Catalytic Information from CSA

site_id	CSA1
Number of Residues	4
Details	Annotated By Reference To The Literature 1bzc

Chain	Residue	Details
A	ARG221
A	ASP181
A	CYS215
A	SER222

---

site_id	MCSA1
Number of Residues	5
Details	M-CSA 469

Chain	Residue	Details
A	ASP181	proton shuttle (general acid/base)
A	CYS215	covalent catalysis
A	ARG221	activator, electrostatic stabiliser
A	SER222	activator, electrostatic stabiliser
A	GLN262	steric role

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