5J87

Discovery of N-(3-(5-((3-acrylamido-4-(morpholine-4-carbonyl)phenyl)amino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-methylphenyl)-4-(tert-butyl)benzamide (CHMFL-BTK-01) as a Highly Selective Irreversible BTK Kinase Inhibitor

Functional Information from GO Data

Chain	GOid	namespace	contents
A	0004672	molecular_function	protein kinase activity
A	0004713	molecular_function	protein tyrosine kinase activity
A	0005524	molecular_function	ATP binding
A	0006468	biological_process	protein phosphorylation
B	0004672	molecular_function	protein kinase activity
B	0004713	molecular_function	protein tyrosine kinase activity
B	0005524	molecular_function	ATP binding
B	0006468	biological_process	protein phosphorylation
C	0004672	molecular_function	protein kinase activity
C	0004713	molecular_function	protein tyrosine kinase activity
C	0005524	molecular_function	ATP binding
C	0006468	biological_process	protein phosphorylation
D	0004672	molecular_function	protein kinase activity
D	0004713	molecular_function	protein tyrosine kinase activity
D	0005524	molecular_function	ATP binding
D	0006468	biological_process	protein phosphorylation

Functional Information from PDB Data

site_id	AC1
Number of Residues	17
Details	binding site for residue N42 A 701

Chain	Residue
A	LEU408
A	ALA478
A	GLY480
A	CYS481
A	ASN526
A	LEU528
A	ASP539
A	HOH828
A	HOH890
A	PHE413
A	VAL416
A	ALA428
A	LYS430
A	THR474
A	GLU475
A	TYR476
A	MET477

---

site_id	AC2
Number of Residues	24
Details	binding site for Di-peptide N42 B 701 and CYS B 481

Chain	Residue
B	LEU408
B	GLY411
B	VAL416
B	ALA428
B	LYS430
B	THR474
B	GLU475
B	TYR476
B	MET477
B	ALA478
B	ASN479
B	GLY480
B	LEU482
B	LEU483
B	ASN484
B	TYR485
B	ASN526
B	LEU528
B	ASP539
B	TYR551
B	HOH819
B	HOH855
B	HOH910
B	HOH926

---

site_id	AC3
Number of Residues	22
Details	binding site for Di-peptide N42 C 701 and CYS C 481

Chain	Residue
C	LEU408
C	GLY411
C	VAL416
C	ALA428
C	LYS430
C	THR474
C	GLU475
C	TYR476
C	MET477
C	ASN479
C	GLY480
C	LEU482
C	LEU483
C	ASN484
C	TYR485
C	ASN526
C	LEU528
C	ASP539
C	HOH803
C	HOH807
C	HOH821
C	HOH827

---

site_id	AC4
Number of Residues	27
Details	binding site for Di-peptide N42 D 701 and CYS D 481

Chain	Residue
D	LEU408
D	THR410
D	GLN412
D	VAL416
D	ALA428
D	LYS430
D	THR474
D	GLU475
D	TYR476
D	MET477
D	ALA478
D	GLY480
D	LEU482
D	LEU483
D	ASN484
D	TYR485
D	ASP521
D	ASN526
D	LEU528
D	ASP539
D	LEU542
D	HOH815
D	HOH854
D	HOH882
D	HOH884
D	HOH902
D	HOH933

---

Functional Information from PROSITE/UniProt

site_id	PS00107
Number of Residues	23
Details	PROTEIN_KINASE_ATP Protein kinases ATP-binding region signature. LGTGQFGVVKyGkwrgqyd...........VAIK

Chain	Residue	Details
A	LEU408-LYS430

---

site_id	PS00109
Number of Residues	13
Details	PROTEIN_KINASE_TYR Tyrosine protein kinases specific active-site signature. FLHrDLAARNCLV

Chain	Residue	Details
A	PHE517-VAL529

---

Functional Information from SwissProt/UniProt

site_id	SWS_FT_FI1
Number of Residues	4
Details	ACT_SITE: Proton acceptor => ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-ProRule:PRU10028

Chain	Residue	Details
A	ASP521
B	ASP521
C	ASP521
D	ASP521

---

site_id	SWS_FT_FI2
Number of Residues	8
Details	BINDING: BINDING => ECO:0000255|PROSITE-ProRule:PRU00159

Chain	Residue	Details
A	LEU408
A	LYS430
B	LEU408
B	LYS430
C	LEU408
C	LYS430
D	LEU408
D	LYS430

---

site_id	SWS_FT_FI3
Number of Residues	4
Details	BINDING: BINDING => ECO:0000269|PubMed:20052711, ECO:0007744|PDB:3K54, ECO:0007744|PDB:3OCT

Chain	Residue	Details
A	THR474
B	THR474
C	THR474
D	THR474

---

site_id	SWS_FT_FI4
Number of Residues	4
Details	BINDING: BINDING => ECO:0000269|PubMed:21280133, ECO:0007744|PDB:3PIY

Chain	Residue	Details
A	LEU542
B	LEU542
C	LEU542
D	LEU542

---

site_id	SWS_FT_FI5
Number of Residues	4
Details	MOD_RES: Phosphotyrosine; by LYN and SYK => ECO:0000269|PubMed:8630736, ECO:0000269|PubMed:9012831

Chain	Residue	Details
A	TYR551
B	TYR551
C	TYR551
D	TYR551

---

site_id	SWS_FT_FI6
Number of Residues	4
Details	MOD_RES: Phosphoserine => ECO:0007744|PubMed:23186163

Chain	Residue	Details
A	SER604
B	SER604
C	SER604
D	SER604

---

site_id	SWS_FT_FI7
Number of Residues	4
Details	MOD_RES: Phosphotyrosine => ECO:0000269|PubMed:15375214

Chain	Residue	Details
A	TYR617
B	TYR617
C	TYR617
D	TYR617

---

site_id	SWS_FT_FI8
Number of Residues	4
Details	MOD_RES: Phosphoserine => ECO:0000269|PubMed:15375214

Chain	Residue	Details
A	SER623
B	SER623
C	SER623
D	SER623

---