6BL0

Novel Modes of Inhibition of Wild-Type IDH1:Direct Covalent Modification of His315 with Cmpd11

Functional Information from GO Data

Chain	GOid	namespace	contents
A	0000287	molecular_function	magnesium ion binding
A	0004450	molecular_function	isocitrate dehydrogenase (NADP+) activity
A	0005515	molecular_function	protein binding
A	0005576	cellular_component	extracellular region
A	0005737	cellular_component	cytoplasm
A	0005739	cellular_component	mitochondrion
A	0005777	cellular_component	peroxisome
A	0005782	cellular_component	peroxisomal matrix
A	0005829	cellular_component	cytosol
A	0006097	biological_process	glyoxylate cycle
A	0006099	biological_process	tricarboxylic acid cycle
A	0006102	biological_process	isocitrate metabolic process
A	0006103	biological_process	2-oxoglutarate metabolic process
A	0006739	biological_process	NADP metabolic process
A	0006749	biological_process	glutathione metabolic process
A	0006979	biological_process	response to oxidative stress
A	0008585	biological_process	female gonad development
A	0014070	biological_process	response to organic cyclic compound
A	0016491	molecular_function	oxidoreductase activity
A	0016616	molecular_function	oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor
A	0034774	cellular_component	secretory granule lumen
A	0042802	molecular_function	identical protein binding
A	0042803	molecular_function	protein homodimerization activity
A	0045296	molecular_function	cadherin binding
A	0046872	molecular_function	metal ion binding
A	0048545	biological_process	response to steroid hormone
A	0050661	molecular_function	NADP binding
A	0051287	molecular_function	NAD binding
A	0060696	biological_process	regulation of phospholipid catabolic process
A	0070062	cellular_component	extracellular exosome
A	0071071	biological_process	regulation of phospholipid biosynthetic process
A	1904724	cellular_component	tertiary granule lumen
A	1904813	cellular_component	ficolin-1-rich granule lumen
B	0000287	molecular_function	magnesium ion binding
B	0004450	molecular_function	isocitrate dehydrogenase (NADP+) activity
B	0005515	molecular_function	protein binding
B	0005576	cellular_component	extracellular region
B	0005737	cellular_component	cytoplasm
B	0005739	cellular_component	mitochondrion
B	0005777	cellular_component	peroxisome
B	0005782	cellular_component	peroxisomal matrix
B	0005829	cellular_component	cytosol
B	0006097	biological_process	glyoxylate cycle
B	0006099	biological_process	tricarboxylic acid cycle
B	0006102	biological_process	isocitrate metabolic process
B	0006103	biological_process	2-oxoglutarate metabolic process
B	0006739	biological_process	NADP metabolic process
B	0006749	biological_process	glutathione metabolic process
B	0006979	biological_process	response to oxidative stress
B	0008585	biological_process	female gonad development
B	0014070	biological_process	response to organic cyclic compound
B	0016491	molecular_function	oxidoreductase activity
B	0016616	molecular_function	oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor
B	0034774	cellular_component	secretory granule lumen
B	0042802	molecular_function	identical protein binding
B	0042803	molecular_function	protein homodimerization activity
B	0045296	molecular_function	cadherin binding
B	0046872	molecular_function	metal ion binding
B	0048545	biological_process	response to steroid hormone
B	0050661	molecular_function	NADP binding
B	0051287	molecular_function	NAD binding
B	0060696	biological_process	regulation of phospholipid catabolic process
B	0070062	cellular_component	extracellular exosome
B	0071071	biological_process	regulation of phospholipid biosynthetic process
B	1904724	cellular_component	tertiary granule lumen
B	1904813	cellular_component	ficolin-1-rich granule lumen
C	0000287	molecular_function	magnesium ion binding
C	0004450	molecular_function	isocitrate dehydrogenase (NADP+) activity
C	0005515	molecular_function	protein binding
C	0005576	cellular_component	extracellular region
C	0005737	cellular_component	cytoplasm
C	0005739	cellular_component	mitochondrion
C	0005777	cellular_component	peroxisome
C	0005782	cellular_component	peroxisomal matrix
C	0005829	cellular_component	cytosol
C	0006097	biological_process	glyoxylate cycle
C	0006099	biological_process	tricarboxylic acid cycle
C	0006102	biological_process	isocitrate metabolic process
C	0006103	biological_process	2-oxoglutarate metabolic process
C	0006739	biological_process	NADP metabolic process
C	0006749	biological_process	glutathione metabolic process
C	0006979	biological_process	response to oxidative stress
C	0008585	biological_process	female gonad development
C	0014070	biological_process	response to organic cyclic compound
C	0016491	molecular_function	oxidoreductase activity
C	0016616	molecular_function	oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor
C	0034774	cellular_component	secretory granule lumen
C	0042802	molecular_function	identical protein binding
C	0042803	molecular_function	protein homodimerization activity
C	0045296	molecular_function	cadherin binding
C	0046872	molecular_function	metal ion binding
C	0048545	biological_process	response to steroid hormone
C	0050661	molecular_function	NADP binding
C	0051287	molecular_function	NAD binding
C	0060696	biological_process	regulation of phospholipid catabolic process
C	0070062	cellular_component	extracellular exosome
C	0071071	biological_process	regulation of phospholipid biosynthetic process
C	1904724	cellular_component	tertiary granule lumen
C	1904813	cellular_component	ficolin-1-rich granule lumen

Functional Information from PDB Data

site_id	AC1
Number of Residues	5
Details	binding site for residue MG A 501

Chain	Residue
A	ASP275
A	ICT502
A	HOH624
B	ASP252
B	HOH611

---

site_id	AC2
Number of Residues	12
Details	binding site for residue ICT A 502

Chain	Residue
A	ARG109
A	ARG132
A	ASP275
A	MG501
A	HOH624
B	LYS212
B	ASP252
B	HOH611
A	THR77
A	SER94
A	ASN96
A	ARG100

---

site_id	AC3
Number of Residues	5
Details	binding site for residue MG A 503

Chain	Residue
A	ASP252
A	ICT505
A	HOH631
B	ASP275
B	HOH609

---

site_id	AC4
Number of Residues	14
Details	binding site for residue DWJ A 504

Chain	Residue
A	GLY289
A	HIS309
A	VAL312
A	ARG314
A	HIS315
A	MET318
A	GLU324
A	THR325
A	SER326
A	THR327
A	ASN328
A	LYS374
A	HOH611
A	HOH669

---

site_id	AC5
Number of Residues	17
Details	binding site for residue ICT A 505

Chain	Residue
A	LYS212
A	ILE215
A	ASP252
A	MG503
A	HOH615
A	HOH631
B	THR77
B	SER94
B	ASN96
B	ARG100
B	ARG109
B	ARG132
B	TYR139
B	ASP275
B	NAP501
B	HOH609
B	HOH618

---

site_id	AC6
Number of Residues	31
Details	binding site for residue NAP B 501

Chain	Residue
A	LEU250
A	ASP253
A	GLN257
A	LYS260
A	ICT505
A	HOH607
A	HOH609
B	LYS72
B	ALA74
B	THR75
B	ILE76
B	THR77
B	ARG82
B	ASN96
B	LEU288
B	GLY289
B	HIS309
B	GLY310
B	THR311
B	VAL312
B	THR313
B	ARG314
B	HIS315
B	ASN328
B	HOH604
B	HOH614
B	HOH618
B	HOH621
B	HOH636
B	HOH642
B	HOH691

---

site_id	AC7
Number of Residues	5
Details	binding site for residue MG C 500

Chain	Residue
C	ASP252
C	ASP275
C	ICT501
C	HOH606
C	HOH632

---

site_id	AC8
Number of Residues	17
Details	binding site for residue ICT C 501

Chain	Residue
C	ASP275
C	MG500
C	NAP502
C	HOH606
C	HOH632
C	HOH633
C	HOH664
C	THR77
C	SER94
C	ASN96
C	ARG100
C	ARG109
C	ARG132
C	TYR139
C	LYS212
C	ILE215
C	ASP252

---

site_id	AC9
Number of Residues	31
Details	binding site for residue NAP C 502

Chain	Residue
C	LYS72
C	ALA74
C	THR75
C	ILE76
C	THR77
C	ARG82
C	ASN96
C	LEU250
C	ASP253
C	LYS260
C	LEU288
C	GLU306
C	ALA307
C	ALA308
C	HIS309
C	GLY310
C	THR311
C	VAL312
C	THR313
C	ARG314
C	HIS315
C	ASN328
C	ICT501
C	HOH601
C	HOH613
C	HOH633
C	HOH650
C	HOH678
C	HOH690
C	HOH698
C	HOH722

---

Functional Information from PROSITE/UniProt

site_id	PS00470
Number of Residues	20
Details	IDH_IMDH Isocitrate and isopropylmalate dehydrogenases signature. NYDGDVqSDsvAqgy.GSLGM

Chain	Residue	Details
A	ASN271-MET290

---

Functional Information from SwissProt/UniProt

site_id	SWS_FT_FI1
Number of Residues	9
Details	BINDING: BINDING => ECO:0000269|PubMed:15173171, ECO:0000269|PubMed:19935646, ECO:0007744|PDB:1T09, ECO:0007744|PDB:1T0L, ECO:0007744|PDB:3INM, ECO:0007744|PDB:3MAP, ECO:0007744|PDB:3MAR, ECO:0007744|PDB:3MAS, ECO:0007744|PDB:4I3K, ECO:0007744|PDB:4I3L, ECO:0007744|PDB:4KZO, ECO:0007744|PDB:4L03, ECO:0007744|PDB:4L04, ECO:0007744|PDB:4L06, ECO:0007744|PDB:4UMX, ECO:0007744|PDB:4UMY, ECO:0007744|PDB:4XRX, ECO:0007744|PDB:4XS3, ECO:0007744|PDB:5DE1, ECO:0007744|PDB:5L57, ECO:0007744|PDB:5L58, ECO:0007744|PDB:5LGE, ECO:0007744|PDB:5SUN, ECO:0007744|PDB:5SVF, ECO:0007744|PDB:5TQH

Chain	Residue	Details
A	THR75
A	GLY310
A	ASN328
B	THR75
B	GLY310
B	ASN328
C	THR75
C	GLY310
C	ASN328

---

site_id	SWS_FT_FI2
Number of Residues	12
Details	BINDING: in other chain => ECO:0000269|PubMed:15173171, ECO:0007744|PDB:1T0L

Chain	Residue	Details
A	THR77
C	SER94
C	ARG109
C	ARG132
A	SER94
A	ARG109
A	ARG132
B	THR77
B	SER94
B	ARG109
B	ARG132
C	THR77

---

site_id	SWS_FT_FI3
Number of Residues	3
Details	BINDING: BINDING => ECO:0000269|PubMed:15173171, ECO:0000269|PubMed:19935646, ECO:0007744|PDB:1T09, ECO:0007744|PDB:1T0L, ECO:0007744|PDB:3INM, ECO:0007744|PDB:3MAP, ECO:0007744|PDB:3MAR, ECO:0007744|PDB:3MAS, ECO:0007744|PDB:4I3K, ECO:0007744|PDB:4I3L, ECO:0007744|PDB:4KZO, ECO:0007744|PDB:4L03, ECO:0007744|PDB:4L04, ECO:0007744|PDB:4L06, ECO:0007744|PDB:4UMX, ECO:0007744|PDB:4UMY, ECO:0007744|PDB:4XRX, ECO:0007744|PDB:4XS3, ECO:0007744|PDB:5DE1, ECO:0007744|PDB:5L57, ECO:0007744|PDB:5LGE, ECO:0007744|PDB:5SUN, ECO:0007744|PDB:5SVF, ECO:0007744|PDB:5TQH

Chain	Residue	Details
A	ARG82
B	ARG82
C	ARG82

---

site_id	SWS_FT_FI4
Number of Residues	3
Details	BINDING: BINDING => ECO:0000269|PubMed:15173171, ECO:0007744|PDB:1T0L

Chain	Residue	Details
A	LYS212
B	LYS212
C	LYS212

---

site_id	SWS_FT_FI5
Number of Residues	3
Details	BINDING: BINDING => ECO:0000305|PubMed:15173171, ECO:0000305|PubMed:19935646, ECO:0007744|PDB:1T0L, ECO:0007744|PDB:3INM

Chain	Residue	Details
A	ASP252
B	ASP252
C	ASP252

---

site_id	SWS_FT_FI6
Number of Residues	3
Details	BINDING: BINDING => ECO:0000269|PubMed:15173171, ECO:0000269|PubMed:19935646, ECO:0007744|PDB:1T0L, ECO:0007744|PDB:3INM

Chain	Residue	Details
A	LYS260
B	LYS260
C	LYS260

---

site_id	SWS_FT_FI7
Number of Residues	6
Details	BINDING: in other chain => ECO:0000305|PubMed:15173171, ECO:0000305|PubMed:19935646, ECO:0007744|PDB:1T0L, ECO:0007744|PDB:3INM

Chain	Residue	Details
A	ASP275
A	ASP279
B	ASP275
B	ASP279
C	ASP275
C	ASP279

---

site_id	SWS_FT_FI8
Number of Residues	6
Details	SITE: Critical for catalysis

Chain	Residue	Details
A	TYR139
A	LYS212
B	TYR139
B	LYS212
C	TYR139
C	LYS212

---

site_id	SWS_FT_FI9
Number of Residues	3
Details	MOD_RES: N-acetylserine => ECO:0007744|PubMed:22814378

Chain	Residue	Details
A	SER2
B	SER2
C	SER2

---

site_id	SWS_FT_FI10
Number of Residues	3
Details	MOD_RES: Phosphotyrosine => ECO:0007744|PubMed:24275569

Chain	Residue	Details
A	TYR42
B	TYR42
C	TYR42

---

site_id	SWS_FT_FI11
Number of Residues	12
Details	MOD_RES: N6-acetyllysine => ECO:0000250|UniProtKB:O88844

Chain	Residue	Details
A	LYS81
C	LYS224
C	LYS233
C	LYS243
A	LYS224
A	LYS233
A	LYS243
B	LYS81
B	LYS224
B	LYS233
B	LYS243
C	LYS81

---

site_id	SWS_FT_FI12
Number of Residues	6
Details	MOD_RES: N6-succinyllysine => ECO:0000250|UniProtKB:O88844

Chain	Residue	Details
A	LYS126
A	LYS400
B	LYS126
B	LYS400
C	LYS126
C	LYS400

---

site_id	SWS_FT_FI13
Number of Residues	3
Details	MOD_RES: N6-acetyllysine => ECO:0007744|PubMed:19608861

Chain	Residue	Details
A	LYS321
B	LYS321
C	LYS321

---

site_id	SWS_FT_FI14
Number of Residues	3
Details	MOD_RES: Phosphoserine => ECO:0000250|UniProtKB:O88844

Chain	Residue	Details
A	SER389
B	SER389
C	SER389

---