2IB9

Crystallographic and kinetic studies of human mitochondrial acetoacetyl-CoA thiolase (T2): the importance of potassium and chloride for its structure and function

Functional Information from GO Data

Chain	GOid	namespace	contents
A	0001889	biological_process	liver development
A	0003985	molecular_function	acetyl-CoA C-acetyltransferase activity
A	0003988	molecular_function	acetyl-CoA C-acyltransferase activity
A	0005739	cellular_component	mitochondrion
A	0005759	cellular_component	mitochondrial matrix
A	0005783	cellular_component	endoplasmic reticulum
A	0006085	biological_process	acetyl-CoA biosynthetic process
A	0006550	biological_process	isoleucine catabolic process
A	0006631	biological_process	fatty acid metabolic process
A	0006635	biological_process	fatty acid beta-oxidation
A	0009725	biological_process	response to hormone
A	0014070	biological_process	response to organic cyclic compound
A	0015936	biological_process	coenzyme A metabolic process
A	0015937	biological_process	coenzyme A biosynthetic process
A	0016453	molecular_function	C-acetyltransferase activity
A	0016746	molecular_function	acyltransferase activity
A	0016747	molecular_function	acyltransferase activity, transferring groups other than amino-acyl groups
A	0019899	molecular_function	enzyme binding
A	0030955	molecular_function	potassium ion binding
A	0034736	molecular_function	cholesterol O-acyltransferase activity
A	0042594	biological_process	response to starvation
A	0042802	molecular_function	identical protein binding
A	0046356	biological_process	acetyl-CoA catabolic process
A	0046872	molecular_function	metal ion binding
A	0046952	biological_process	ketone body catabolic process
A	0060612	biological_process	adipose tissue development
A	0070062	cellular_component	extracellular exosome
A	0072229	biological_process	metanephric proximal convoluted tubule development
A	0120225	molecular_function	coenzyme A binding
A	1902224	biological_process	ketone body metabolic process
A	1902860	biological_process	propionyl-CoA biosynthetic process
B	0001889	biological_process	liver development
B	0003985	molecular_function	acetyl-CoA C-acetyltransferase activity
B	0003988	molecular_function	acetyl-CoA C-acyltransferase activity
B	0005739	cellular_component	mitochondrion
B	0005759	cellular_component	mitochondrial matrix
B	0005783	cellular_component	endoplasmic reticulum
B	0006085	biological_process	acetyl-CoA biosynthetic process
B	0006550	biological_process	isoleucine catabolic process
B	0006631	biological_process	fatty acid metabolic process
B	0006635	biological_process	fatty acid beta-oxidation
B	0009725	biological_process	response to hormone
B	0014070	biological_process	response to organic cyclic compound
B	0015936	biological_process	coenzyme A metabolic process
B	0015937	biological_process	coenzyme A biosynthetic process
B	0016453	molecular_function	C-acetyltransferase activity
B	0016746	molecular_function	acyltransferase activity
B	0016747	molecular_function	acyltransferase activity, transferring groups other than amino-acyl groups
B	0019899	molecular_function	enzyme binding
B	0030955	molecular_function	potassium ion binding
B	0034736	molecular_function	cholesterol O-acyltransferase activity
B	0042594	biological_process	response to starvation
B	0042802	molecular_function	identical protein binding
B	0046356	biological_process	acetyl-CoA catabolic process
B	0046872	molecular_function	metal ion binding
B	0046952	biological_process	ketone body catabolic process
B	0060612	biological_process	adipose tissue development
B	0070062	cellular_component	extracellular exosome
B	0072229	biological_process	metanephric proximal convoluted tubule development
B	0120225	molecular_function	coenzyme A binding
B	1902224	biological_process	ketone body metabolic process
B	1902860	biological_process	propionyl-CoA biosynthetic process
C	0001889	biological_process	liver development
C	0003985	molecular_function	acetyl-CoA C-acetyltransferase activity
C	0003988	molecular_function	acetyl-CoA C-acyltransferase activity
C	0005739	cellular_component	mitochondrion
C	0005759	cellular_component	mitochondrial matrix
C	0005783	cellular_component	endoplasmic reticulum
C	0006085	biological_process	acetyl-CoA biosynthetic process
C	0006550	biological_process	isoleucine catabolic process
C	0006631	biological_process	fatty acid metabolic process
C	0006635	biological_process	fatty acid beta-oxidation
C	0009725	biological_process	response to hormone
C	0014070	biological_process	response to organic cyclic compound
C	0015936	biological_process	coenzyme A metabolic process
C	0015937	biological_process	coenzyme A biosynthetic process
C	0016453	molecular_function	C-acetyltransferase activity
C	0016746	molecular_function	acyltransferase activity
C	0016747	molecular_function	acyltransferase activity, transferring groups other than amino-acyl groups
C	0019899	molecular_function	enzyme binding
C	0030955	molecular_function	potassium ion binding
C	0034736	molecular_function	cholesterol O-acyltransferase activity
C	0042594	biological_process	response to starvation
C	0042802	molecular_function	identical protein binding
C	0046356	biological_process	acetyl-CoA catabolic process
C	0046872	molecular_function	metal ion binding
C	0046952	biological_process	ketone body catabolic process
C	0060612	biological_process	adipose tissue development
C	0070062	cellular_component	extracellular exosome
C	0072229	biological_process	metanephric proximal convoluted tubule development
C	0120225	molecular_function	coenzyme A binding
C	1902224	biological_process	ketone body metabolic process
C	1902860	biological_process	propionyl-CoA biosynthetic process
D	0001889	biological_process	liver development
D	0003985	molecular_function	acetyl-CoA C-acetyltransferase activity
D	0003988	molecular_function	acetyl-CoA C-acyltransferase activity
D	0005739	cellular_component	mitochondrion
D	0005759	cellular_component	mitochondrial matrix
D	0005783	cellular_component	endoplasmic reticulum
D	0006085	biological_process	acetyl-CoA biosynthetic process
D	0006550	biological_process	isoleucine catabolic process
D	0006631	biological_process	fatty acid metabolic process
D	0006635	biological_process	fatty acid beta-oxidation
D	0009725	biological_process	response to hormone
D	0014070	biological_process	response to organic cyclic compound
D	0015936	biological_process	coenzyme A metabolic process
D	0015937	biological_process	coenzyme A biosynthetic process
D	0016453	molecular_function	C-acetyltransferase activity
D	0016746	molecular_function	acyltransferase activity
D	0016747	molecular_function	acyltransferase activity, transferring groups other than amino-acyl groups
D	0019899	molecular_function	enzyme binding
D	0030955	molecular_function	potassium ion binding
D	0034736	molecular_function	cholesterol O-acyltransferase activity
D	0042594	biological_process	response to starvation
D	0042802	molecular_function	identical protein binding
D	0046356	biological_process	acetyl-CoA catabolic process
D	0046872	molecular_function	metal ion binding
D	0046952	biological_process	ketone body catabolic process
D	0060612	biological_process	adipose tissue development
D	0070062	cellular_component	extracellular exosome
D	0072229	biological_process	metanephric proximal convoluted tubule development
D	0120225	molecular_function	coenzyme A binding
D	1902224	biological_process	ketone body metabolic process
D	1902860	biological_process	propionyl-CoA biosynthetic process

Functional Information from PDB Data

site_id	AC1
Number of Residues	3
Details	BINDING SITE FOR RESIDUE CL B 2001

Chain	Residue
A	ASN414
A	GLY418
B	CYS119

---

site_id	AC2
Number of Residues	2
Details	BINDING SITE FOR RESIDUE CL A 2002

Chain	Residue
A	CYS119
B	ASN414

---

site_id	AC3
Number of Residues	2
Details	BINDING SITE FOR RESIDUE CL D 2003

Chain	Residue
C	ASN414
D	CYS119

---

site_id	AC4
Number of Residues	3
Details	BINDING SITE FOR RESIDUE CL C 2004

Chain	Residue
D	HOH5086
C	CYS119
D	ASN414

---

site_id	AC5
Number of Residues	6
Details	BINDING SITE FOR RESIDUE K A 3001

Chain	Residue
A	TYR219
A	ALA280
A	ALA281
A	ALA283
A	VAL381
A	HOH5101

---

site_id	AC6
Number of Residues	6
Details	BINDING SITE FOR RESIDUE K B 3002

Chain	Residue
B	TYR219
B	ALA280
B	ALA281
B	ALA283
B	VAL381
B	HOH5071

---

site_id	AC7
Number of Residues	6
Details	BINDING SITE FOR RESIDUE K C 3003

Chain	Residue
C	TYR219
C	ALA280
C	ALA281
C	ALA283
C	VAL381
C	HOH5050

---

site_id	AC8
Number of Residues	6
Details	BINDING SITE FOR RESIDUE K D 3004

Chain	Residue
D	TYR219
D	ALA280
D	ALA281
D	ALA283
D	VAL381
D	HOH5042

---

site_id	AC9
Number of Residues	4
Details	BINDING SITE FOR RESIDUE MES A 5001

Chain	Residue
A	PHE55
A	LEU56
A	LEU286
B	HOH5032

---

site_id	BC1
Number of Residues	4
Details	BINDING SITE FOR RESIDUE MES B 5002

Chain	Residue
B	PHE55
B	LEU56
D	TYR170
D	HOH5104

---

site_id	BC2
Number of Residues	3
Details	BINDING SITE FOR RESIDUE MES C 5003

Chain	Residue
A	TYR170
C	PHE55
C	LEU56

---

site_id	BC3
Number of Residues	1
Details	BINDING SITE FOR RESIDUE MES D 5004

Chain	Residue
D	PHE55

---

site_id	BC4
Number of Residues	6
Details	BINDING SITE FOR RESIDUE GOL A 4001

Chain	Residue
A	LEU184
A	SER284
A	PHE356
A	HOH5039
A	HOH5213
A	HOH5276

---

site_id	BC5
Number of Residues	3
Details	BINDING SITE FOR RESIDUE GOL B 4002

Chain	Residue
B	SER284
B	THR285
B	HOH5048

---

site_id	BC6
Number of Residues	7
Details	BINDING SITE FOR RESIDUE GOL A 4003

Chain	Residue
A	ALA201
A	ASN205
A	ILE206
A	THR277
A	HOH5120
A	HOH5150
A	HOH5196

---

site_id	BC7
Number of Residues	2
Details	BINDING SITE FOR RESIDUE GOL A 4004

Chain	Residue
A	VAL270
A	HOH5198

---

site_id	BC8
Number of Residues	3
Details	BINDING SITE FOR RESIDUE GOL C 4005

Chain	Residue
C	SER284
C	THR285
C	HOH5020

---

Functional Information from PROSITE/UniProt

site_id	PS00098
Number of Residues	19
Details	THIOLASE_1 Thiolases acyl-enzyme intermediate signature. INKvCASGMkAImmasqsL

Chain	Residue	Details
A	ILE122-LEU140

---

site_id	PS00099
Number of Residues	14
Details	THIOLASE_3 Thiolases active site. GLASICNGgGgAsA

Chain	Residue	Details
A	GLY408-ALA421

---

site_id	PS00737
Number of Residues	17
Details	THIOLASE_2 Thiolases signature 2. NinGGaVSlGHPiGmSG

Chain	Residue	Details
A	ASN375-GLY391

---

Functional Information from SwissProt/UniProt

site_id	SWS_FT_FI1
Number of Residues	4
Details	ACT_SITE: Acyl-thioester intermediate => ECO:0000305|PubMed:17371050

Chain	Residue	Details
A	CYS126
B	CYS126
C	CYS126
D	CYS126

---

site_id	SWS_FT_FI2
Number of Residues	4
Details	ACT_SITE: Proton donor/acceptor => ECO:0000305|PubMed:17371050

Chain	Residue	Details
A	CYS413
B	CYS413
C	CYS413
D	CYS413

---

site_id	SWS_FT_FI3
Number of Residues	32
Details	BINDING: BINDING => ECO:0000269|PubMed:17371050

Chain	Residue	Details
A	TYR219
A	ALA281
A	ALA283
A	SER284
A	VAL381
B	TYR219
B	ARG258
B	LYS263
B	ALA280
B	ALA281
B	ALA283
B	SER284
B	VAL381
C	TYR219
C	ARG258
C	LYS263
C	ALA280
C	ALA281
C	ALA283
C	SER284
C	VAL381
D	TYR219
D	ARG258
D	LYS263
D	ALA280
D	ALA281
D	ALA283
D	SER284
D	VAL381
A	ARG258
A	LYS263
A	ALA280

---

site_id	SWS_FT_FI4
Number of Residues	4
Details	SITE: Increases nucleophilicity of active site Cys => ECO:0000305|PubMed:17371050

Chain	Residue	Details
A	HIS385
B	HIS385
C	HIS385
D	HIS385

---

site_id	SWS_FT_FI5
Number of Residues	32
Details	MOD_RES: N6-succinyllysine; alternate => ECO:0000250|UniProtKB:Q8QZT1

Chain	Residue	Details
B	LYS202
B	LYS223
B	LYS230
B	LYS263
C	LYS66
C	LYS174
C	LYS181
C	LYS190
C	LYS202
C	LYS223
C	LYS230
C	LYS263
D	LYS66
D	LYS174
D	LYS181
D	LYS190
D	LYS202
D	LYS223
D	LYS230
D	LYS263
A	LYS66
A	LYS174
A	LYS181
A	LYS190
A	LYS202
A	LYS223
A	LYS230
A	LYS263
B	LYS66
B	LYS174
B	LYS181
B	LYS190

---

site_id	SWS_FT_FI6
Number of Residues	16
Details	MOD_RES: N6-succinyllysine => ECO:0000250|UniProtKB:Q8QZT1

Chain	Residue	Details
B	LYS78
B	LYS243
B	LYS266
B	LYS268
C	LYS78
C	LYS243
C	LYS266
C	LYS268
D	LYS78
D	LYS243
D	LYS266
D	LYS268
A	LYS78
A	LYS243
A	LYS266
A	LYS268

---

site_id	SWS_FT_FI7
Number of Residues	4
Details	MOD_RES: N6-acetyllysine => ECO:0007744|PubMed:19608861

Chain	Residue	Details
A	LYS251
B	LYS251
C	LYS251
D	LYS251

---

site_id	SWS_FT_FI8
Number of Residues	12
Details	MOD_RES: N6-acetyllysine => ECO:0000250|UniProtKB:Q8QZT1

Chain	Residue	Details
A	LYS257
A	LYS273
A	LYS338
B	LYS257
B	LYS273
B	LYS338
C	LYS257
C	LYS273
C	LYS338
D	LYS257
D	LYS273
D	LYS338

---