6XIH

Structure-guided optimization of a novel class of ASK1 inhibitors with increased sp3 character and an exquisite selectivity profile

Functional Information from GO Data

Chain	GOid	namespace	contents
A	0004672	molecular_function	protein kinase activity
A	0005524	molecular_function	ATP binding
A	0006468	biological_process	protein phosphorylation
B	0004672	molecular_function	protein kinase activity
B	0005524	molecular_function	ATP binding
B	0006468	biological_process	protein phosphorylation

Functional Information from PDB Data

site_id	AC1
Number of Residues	14
Details	binding site for residue V3S A 1000

Chain	Residue
A	LEU686
A	GLY759
A	ASP807
A	LEU810
A	SER821
A	ASP822
A	VAL694
A	ALA707
A	LYS709
A	VAL738
A	MET754
A	GLU755
A	GLN756
A	VAL757

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site_id	AC2
Number of Residues	16
Details	binding site for residue V3S B 1000

Chain	Residue
B	LEU686
B	LYS688
B	GLY689
B	VAL694
B	ALA707
B	LYS709
B	VAL738
B	MET754
B	GLU755
B	GLN756
B	VAL757
B	GLY760
B	ASP807
B	LEU810
B	SER821
B	HOH1107

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Functional Information from PROSITE/UniProt

site_id	PS00107
Number of Residues	24
Details	PROTEIN_KINASE_ATP Protein kinases ATP-binding region signature. LGKGTYGIVYaGrdlsnqvr..........IAIK

Chain	Residue	Details
A	LEU686-LYS709

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site_id	PS00108
Number of Residues	13
Details	PROTEIN_KINASE_ST Serine/Threonine protein kinases active-site signature. IvHrDIKgdNVLI

Chain	Residue	Details
A	ILE799-ILE811

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Functional Information from SwissProt/UniProt

site_id	SWS_FT_FI1
Number of Residues	2
Details	ACT_SITE: Proton acceptor => ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-ProRule:PRU10027

Chain	Residue	Details
A	ASP803
B	ASP803

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site_id	SWS_FT_FI2
Number of Residues	2
Details	BINDING: BINDING => ECO:0000255|PROSITE-ProRule:PRU00159

Chain	Residue	Details
A	LEU686
B	LEU686

---

site_id	SWS_FT_FI3
Number of Residues	2
Details	BINDING:

Chain	Residue	Details
A	LYS709
B	LYS709

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site_id	SWS_FT_FI4
Number of Residues	2
Details	MOD_RES: Phosphotyrosine => ECO:0000269|PubMed:16407264

Chain	Residue	Details
A	TYR718
B	TYR718

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site_id	SWS_FT_FI5
Number of Residues	4
Details	MOD_RES: Phosphothreonine; by autocatalysis => ECO:0000269|PubMed:17937911

Chain	Residue	Details
A	THR813
A	THR842
B	THR813
B	THR842

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site_id	SWS_FT_FI6
Number of Residues	2
Details	MOD_RES: Phosphothreonine; by autocatalysis, MELK and MAP3K6 => ECO:0000269|PubMed:11920685, ECO:0000269|PubMed:17210579, ECO:0000269|PubMed:17937911, ECO:0000269|PubMed:18948261, ECO:0000269|PubMed:19590015, ECO:0000269|PubMed:23102700

Chain	Residue	Details
A	THR838
B	THR838

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