6SBV

X-ray Structure of Human LDH-A with an Allosteric Inhibitor (Compound 7)

Functional Information from GO Data

Chain	GOid	namespace	contents
A	0003824	molecular_function	catalytic activity
A	0004459	molecular_function	L-lactate dehydrogenase activity
A	0005515	molecular_function	protein binding
A	0005634	cellular_component	nucleus
A	0005737	cellular_component	cytoplasm
A	0005739	cellular_component	mitochondrion
A	0005829	cellular_component	cytosol
A	0006089	biological_process	lactate metabolic process
A	0006090	biological_process	pyruvate metabolic process
A	0006096	biological_process	glycolytic process
A	0016020	cellular_component	membrane
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	0019752	biological_process	carboxylic acid metabolic process
A	0042802	molecular_function	identical protein binding
A	0045296	molecular_function	cadherin binding
A	0070062	cellular_component	extracellular exosome
A	1990204	cellular_component	oxidoreductase complex
B	0003824	molecular_function	catalytic activity
B	0004459	molecular_function	L-lactate dehydrogenase activity
B	0005515	molecular_function	protein binding
B	0005634	cellular_component	nucleus
B	0005737	cellular_component	cytoplasm
B	0005739	cellular_component	mitochondrion
B	0005829	cellular_component	cytosol
B	0006089	biological_process	lactate metabolic process
B	0006090	biological_process	pyruvate metabolic process
B	0006096	biological_process	glycolytic process
B	0016020	cellular_component	membrane
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	0019752	biological_process	carboxylic acid metabolic process
B	0042802	molecular_function	identical protein binding
B	0045296	molecular_function	cadherin binding
B	0070062	cellular_component	extracellular exosome
B	1990204	cellular_component	oxidoreductase complex
C	0003824	molecular_function	catalytic activity
C	0004459	molecular_function	L-lactate dehydrogenase activity
C	0005515	molecular_function	protein binding
C	0005634	cellular_component	nucleus
C	0005737	cellular_component	cytoplasm
C	0005739	cellular_component	mitochondrion
C	0005829	cellular_component	cytosol
C	0006089	biological_process	lactate metabolic process
C	0006090	biological_process	pyruvate metabolic process
C	0006096	biological_process	glycolytic process
C	0016020	cellular_component	membrane
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	0019752	biological_process	carboxylic acid metabolic process
C	0042802	molecular_function	identical protein binding
C	0045296	molecular_function	cadherin binding
C	0070062	cellular_component	extracellular exosome
C	1990204	cellular_component	oxidoreductase complex
D	0003824	molecular_function	catalytic activity
D	0004459	molecular_function	L-lactate dehydrogenase activity
D	0005515	molecular_function	protein binding
D	0005634	cellular_component	nucleus
D	0005737	cellular_component	cytoplasm
D	0005739	cellular_component	mitochondrion
D	0005829	cellular_component	cytosol
D	0006089	biological_process	lactate metabolic process
D	0006090	biological_process	pyruvate metabolic process
D	0006096	biological_process	glycolytic process
D	0016020	cellular_component	membrane
D	0016491	molecular_function	oxidoreductase activity
D	0016616	molecular_function	oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor
D	0019752	biological_process	carboxylic acid metabolic process
D	0042802	molecular_function	identical protein binding
D	0045296	molecular_function	cadherin binding
D	0070062	cellular_component	extracellular exosome
D	1990204	cellular_component	oxidoreductase complex
E	0003824	molecular_function	catalytic activity
E	0004459	molecular_function	L-lactate dehydrogenase activity
E	0005515	molecular_function	protein binding
E	0005634	cellular_component	nucleus
E	0005737	cellular_component	cytoplasm
E	0005739	cellular_component	mitochondrion
E	0005829	cellular_component	cytosol
E	0006089	biological_process	lactate metabolic process
E	0006090	biological_process	pyruvate metabolic process
E	0006096	biological_process	glycolytic process
E	0016020	cellular_component	membrane
E	0016491	molecular_function	oxidoreductase activity
E	0016616	molecular_function	oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor
E	0019752	biological_process	carboxylic acid metabolic process
E	0042802	molecular_function	identical protein binding
E	0045296	molecular_function	cadherin binding
E	0070062	cellular_component	extracellular exosome
E	1990204	cellular_component	oxidoreductase complex
F	0003824	molecular_function	catalytic activity
F	0004459	molecular_function	L-lactate dehydrogenase activity
F	0005515	molecular_function	protein binding
F	0005634	cellular_component	nucleus
F	0005737	cellular_component	cytoplasm
F	0005739	cellular_component	mitochondrion
F	0005829	cellular_component	cytosol
F	0006089	biological_process	lactate metabolic process
F	0006090	biological_process	pyruvate metabolic process
F	0006096	biological_process	glycolytic process
F	0016020	cellular_component	membrane
F	0016491	molecular_function	oxidoreductase activity
F	0016616	molecular_function	oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor
F	0019752	biological_process	carboxylic acid metabolic process
F	0042802	molecular_function	identical protein binding
F	0045296	molecular_function	cadherin binding
F	0070062	cellular_component	extracellular exosome
F	1990204	cellular_component	oxidoreductase complex
G	0003824	molecular_function	catalytic activity
G	0004459	molecular_function	L-lactate dehydrogenase activity
G	0005515	molecular_function	protein binding
G	0005634	cellular_component	nucleus
G	0005737	cellular_component	cytoplasm
G	0005739	cellular_component	mitochondrion
G	0005829	cellular_component	cytosol
G	0006089	biological_process	lactate metabolic process
G	0006090	biological_process	pyruvate metabolic process
G	0006096	biological_process	glycolytic process
G	0016020	cellular_component	membrane
G	0016491	molecular_function	oxidoreductase activity
G	0016616	molecular_function	oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor
G	0019752	biological_process	carboxylic acid metabolic process
G	0042802	molecular_function	identical protein binding
G	0045296	molecular_function	cadherin binding
G	0070062	cellular_component	extracellular exosome
G	1990204	cellular_component	oxidoreductase complex
H	0003824	molecular_function	catalytic activity
H	0004459	molecular_function	L-lactate dehydrogenase activity
H	0005515	molecular_function	protein binding
H	0005634	cellular_component	nucleus
H	0005737	cellular_component	cytoplasm
H	0005739	cellular_component	mitochondrion
H	0005829	cellular_component	cytosol
H	0006089	biological_process	lactate metabolic process
H	0006090	biological_process	pyruvate metabolic process
H	0006096	biological_process	glycolytic process
H	0016020	cellular_component	membrane
H	0016491	molecular_function	oxidoreductase activity
H	0016616	molecular_function	oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor
H	0019752	biological_process	carboxylic acid metabolic process
H	0042802	molecular_function	identical protein binding
H	0045296	molecular_function	cadherin binding
H	0070062	cellular_component	extracellular exosome
H	1990204	cellular_component	oxidoreductase complex

Functional Information from PDB Data

site_id	AC1
Number of Residues	16
Details	binding site for residue L5K A 1001

Chain	Residue
A	ARG169
B	HIS67
B	LEU70
B	THR74
B	PRO75
B	LYS76
B	ILE77
B	HOH1110
A	TYR172
A	LEU173
A	GLU176
A	VAL180
A	GLN233
A	SER237
A	HOH1116
B	GLN66

---

site_id	AC2
Number of Residues	17
Details	binding site for residue L5K B 1001

Chain	Residue
A	GLN66
A	HIS67
A	LEU70
A	THR74
A	PRO75
A	LYS76
A	ILE77
A	HOH1143
B	ARG169
B	TYR172
B	LEU173
B	GLU176
B	GLY179
B	VAL180
B	GLN233
B	SER237
B	HOH1104

---

site_id	AC3
Number of Residues	14
Details	binding site for residue L5K C 1001

Chain	Residue
C	ARG169
C	TYR172
C	LEU173
C	GLU176
C	VAL180
C	GLN233
C	SER237
C	HOH1112
D	GLN66
D	HIS67
D	LEU70
D	THR74
D	PRO75
D	ILE77

---

site_id	AC4
Number of Residues	15
Details	binding site for residue L5K D 1001

Chain	Residue
C	GLN66
C	HIS67
C	LEU70
C	THR74
C	PRO75
C	LYS76
C	ILE77
D	ARG169
D	TYR172
D	LEU173
D	GLU176
D	VAL180
D	GLN233
D	SER237
D	HOH1114

---

site_id	AC5
Number of Residues	16
Details	binding site for residue L5K E 1001

Chain	Residue
E	ARG169
E	TYR172
E	LEU173
E	GLU176
E	VAL180
E	GLN233
E	SER237
E	HOH1109
E	HOH1139
F	GLN66
F	HIS67
F	LEU70
F	THR74
F	PRO75
F	LYS76
F	ILE77

---

site_id	AC6
Number of Residues	16
Details	binding site for residue L5K F 1001

Chain	Residue
E	GLN66
E	HIS67
E	LEU70
E	THR74
E	PRO75
E	LYS76
E	ILE77
F	ARG169
F	TYR172
F	LEU173
F	GLU176
F	GLY179
F	VAL180
F	SER237
F	HOH1104
F	HOH1137

---

site_id	AC7
Number of Residues	14
Details	binding site for residue L5K G 1001

Chain	Residue
G	GLN233
G	SER237
G	HOH1101
H	GLN66
H	HIS67
H	LEU70
H	THR74
H	PRO75
H	ILE77
E	HOH1128
G	ARG169
G	TYR172
G	LEU173
G	GLU176

---

site_id	AC8
Number of Residues	14
Details	binding site for residue L5K H 1001

Chain	Residue
G	GLN66
G	HIS67
G	LEU70
G	THR74
G	PRO75
G	ILE77
H	ARG169
H	TYR172
H	LEU173
H	GLU176
H	VAL180
H	GLN233
H	SER237
H	HOH1101

---

Functional Information from PROSITE/UniProt

site_id	PS00064
Number of Residues	7
Details	L_LDH L-lactate dehydrogenase active site. LGEHGDS

Chain	Residue	Details
A	LEU190-SER196

---

Functional Information from SwissProt/UniProt

site_id	SWS_FT_FI1
Number of Residues	8
Details	ACT_SITE: Proton acceptor

Chain	Residue	Details
A	HIS193
B	HIS193
C	HIS193
D	HIS193
E	HIS193
F	HIS193
G	HIS193
H	HIS193

---

site_id	SWS_FT_FI2
Number of Residues	16
Details	BINDING: BINDING => ECO:0000269|PubMed:11276087

Chain	Residue	Details
E	GLY29
E	ARG99
F	GLY29
F	ARG99
G	GLY29
G	ARG99
H	GLY29
H	ARG99
A	ARG99
B	GLY29
B	ARG99
C	GLY29
C	ARG99
D	GLY29
D	ARG99
A	GLY29

---

site_id	SWS_FT_FI3
Number of Residues	32
Details	BINDING:

Chain	Residue	Details
C	ARG106
C	ASN138
C	ARG169
C	THR248
D	ARG106
D	ASN138
D	ARG169
D	THR248
E	ARG106
E	ASN138
E	ARG169
E	THR248
F	ARG106
F	ASN138
F	ARG169
F	THR248
G	ARG106
G	ASN138
G	ARG169
G	THR248
H	ARG106
H	ASN138
H	ARG169
H	THR248
A	ASN138
A	ARG169
A	THR248
B	ARG106
B	ASN138
B	ARG169
B	THR248
A	ARG106

---

site_id	SWS_FT_FI4
Number of Residues	8
Details	MOD_RES: N-acetylalanine => ECO:0000269|Ref.10, ECO:0007744|PubMed:19413330, ECO:0007744|PubMed:22223895

Chain	Residue	Details
E	ALA2
F	ALA2
G	ALA2
H	ALA2
A	ALA2
B	ALA2
C	ALA2
D	ALA2

---

site_id	SWS_FT_FI5
Number of Residues	24
Details	MOD_RES: N6-succinyllysine; alternate => ECO:0000250|UniProtKB:P06151

Chain	Residue	Details
C	LYS318
D	LYS5
D	LYS118
D	LYS318
E	LYS5
E	LYS118
E	LYS318
F	LYS5
F	LYS118
F	LYS318
G	LYS5
G	LYS118
G	LYS318
H	LYS5
H	LYS118
H	LYS318
A	LYS118
A	LYS318
B	LYS5
B	LYS118
B	LYS318
C	LYS5
C	LYS118
A	LYS5

---

site_id	SWS_FT_FI6
Number of Residues	8
Details	MOD_RES: Phosphotyrosine => ECO:0007744|PubMed:19690332

Chain	Residue	Details
D	TYR10
E	TYR10
F	TYR10
G	TYR10
H	TYR10
A	TYR10
B	TYR10
C	TYR10

---

site_id	SWS_FT_FI7
Number of Residues	24
Details	MOD_RES: N6-acetyllysine => ECO:0007744|PubMed:19608861

Chain	Residue	Details
C	LYS126
D	LYS14
D	LYS81
D	LYS126
E	LYS14
E	LYS81
E	LYS126
F	LYS14
F	LYS81
F	LYS126
G	LYS14
G	LYS81
G	LYS126
H	LYS14
H	LYS81
H	LYS126
A	LYS81
A	LYS126
B	LYS14
B	LYS81
B	LYS126
C	LYS14
C	LYS81
A	LYS14

---

site_id	SWS_FT_FI8
Number of Residues	8
Details	MOD_RES: Phosphothreonine => ECO:0007744|PubMed:23186163

Chain	Residue	Details
D	THR18
E	THR18
F	THR18
G	THR18
H	THR18
A	THR18
B	THR18
C	THR18

---

site_id	SWS_FT_FI9
Number of Residues	8
Details	MOD_RES: N6-acetyllysine; alternate => ECO:0007744|PubMed:19608861

Chain	Residue	Details
B	LYS57
C	LYS57
D	LYS57
E	LYS57
F	LYS57
G	LYS57
H	LYS57
A	LYS57

---

site_id	SWS_FT_FI10
Number of Residues	24
Details	MOD_RES: N6-acetyllysine => ECO:0000250|UniProtKB:P06151

Chain	Residue	Details
C	LYS243
D	LYS224
D	LYS232
D	LYS243
E	LYS224
E	LYS232
E	LYS243
F	LYS224
F	LYS232
F	LYS243
G	LYS224
G	LYS232
G	LYS243
H	LYS224
H	LYS232
H	LYS243
A	LYS232
A	LYS243
B	LYS224
B	LYS232
B	LYS243
C	LYS224
C	LYS232
A	LYS224

---

site_id	SWS_FT_FI11
Number of Residues	8
Details	MOD_RES: Phosphotyrosine => ECO:0000250|UniProtKB:P06151

Chain	Residue	Details
A	TYR239
B	TYR239
C	TYR239
D	TYR239
E	TYR239
F	TYR239
G	TYR239
H	TYR239

---

site_id	SWS_FT_FI12
Number of Residues	16
Details	MOD_RES: Phosphothreonine => ECO:0000250|UniProtKB:P04642

Chain	Residue	Details
E	THR309
E	THR322
F	THR309
F	THR322
G	THR309
G	THR322
H	THR309
H	THR322
A	THR309
A	THR322
B	THR309
B	THR322
C	THR309
C	THR322
D	THR309
D	THR322

---

site_id	SWS_FT_FI13
Number of Residues	8
Details	MOD_RES: Phosphoserine => ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569

Chain	Residue	Details
A	SER310
B	SER310
C	SER310
D	SER310
E	SER310
F	SER310
G	SER310
H	SER310

---

site_id	SWS_FT_FI14
Number of Residues	16
Details	CROSSLNK: Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternate => ECO:0007744|PubMed:28112733

Chain	Residue	Details
E	LYS57
F	LYS57
G	LYS57
H	LYS57
A	LYS57
B	LYS57
C	LYS57
D	LYS57

---