1GG5

CRYSTAL STRUCTURE OF A COMPLEX OF HUMAN NAD[P]H-QUINONE OXIDOREDUCTASE AND A CHEMOTHERAPEUTIC DRUG (E09) AT 2.5 A RESOLUTION

Functional Information from GO Data

Chain	GOid	namespace	contents
A	0000209	biological_process	protein polyubiquitination
A	0002931	biological_process	response to ischemia
A	0003723	molecular_function	RNA binding
A	0003955	molecular_function	NAD(P)H dehydrogenase (quinone) activity
A	0004128	molecular_function	cytochrome-b5 reductase activity, acting on NAD(P)H
A	0004784	molecular_function	superoxide dismutase activity
A	0005515	molecular_function	protein binding
A	0005634	cellular_component	nucleus
A	0005737	cellular_component	cytoplasm
A	0005829	cellular_component	cytosol
A	0006116	biological_process	NADH oxidation
A	0006743	biological_process	ubiquinone metabolic process
A	0006801	biological_process	superoxide metabolic process
A	0006805	biological_process	xenobiotic metabolic process
A	0006809	biological_process	nitric oxide biosynthetic process
A	0006979	biological_process	response to oxidative stress
A	0007271	biological_process	synaptic transmission, cholinergic
A	0007584	biological_process	response to nutrient
A	0008753	molecular_function	NADPH dehydrogenase (quinone) activity
A	0009410	biological_process	response to xenobiotic stimulus
A	0009636	biological_process	response to toxic substance
A	0009725	biological_process	response to hormone
A	0009743	biological_process	response to carbohydrate
A	0010033	biological_process	response to organic substance
A	0014070	biological_process	response to organic cyclic compound
A	0014075	biological_process	response to amine
A	0016491	molecular_function	oxidoreductase activity
A	0019430	biological_process	removal of superoxide radicals
A	0030163	biological_process	protein catabolic process
A	0030425	cellular_component	dendrite
A	0032355	biological_process	response to estradiol
A	0032496	biological_process	response to lipopolysaccharide
A	0033574	biological_process	response to testosterone
A	0034599	biological_process	cellular response to oxidative stress
A	0042177	biological_process	negative regulation of protein catabolic process
A	0042360	biological_process	vitamin E metabolic process
A	0042373	biological_process	vitamin K metabolic process
A	0042802	molecular_function	identical protein binding
A	0043025	cellular_component	neuronal cell body
A	0043066	biological_process	negative regulation of apoptotic process
A	0043279	biological_process	response to alkaloid
A	0043525	biological_process	positive regulation of neuron apoptotic process
A	0045087	biological_process	innate immune response
A	0045202	cellular_component	synapse
A	0045454	biological_process	cell redox homeostasis
A	0045471	biological_process	response to ethanol
A	0050136	molecular_function	NADH:ubiquinone reductase (non-electrogenic) activity
A	0051602	biological_process	response to electrical stimulus
A	0070301	biological_process	cellular response to hydrogen peroxide
A	0070995	biological_process	NADPH oxidation
A	0071248	biological_process	cellular response to metal ion
A	1901698	biological_process	response to nitrogen compound
A	1904772	biological_process	response to tetrachloromethane
A	1904844	biological_process	response to L-glutamine
A	1904880	biological_process	response to hydrogen sulfide
A	1905395	biological_process	response to flavonoid
B	0000209	biological_process	protein polyubiquitination
B	0002931	biological_process	response to ischemia
B	0003723	molecular_function	RNA binding
B	0003955	molecular_function	NAD(P)H dehydrogenase (quinone) activity
B	0004128	molecular_function	cytochrome-b5 reductase activity, acting on NAD(P)H
B	0004784	molecular_function	superoxide dismutase activity
B	0005515	molecular_function	protein binding
B	0005634	cellular_component	nucleus
B	0005737	cellular_component	cytoplasm
B	0005829	cellular_component	cytosol
B	0006116	biological_process	NADH oxidation
B	0006743	biological_process	ubiquinone metabolic process
B	0006801	biological_process	superoxide metabolic process
B	0006805	biological_process	xenobiotic metabolic process
B	0006809	biological_process	nitric oxide biosynthetic process
B	0006979	biological_process	response to oxidative stress
B	0007271	biological_process	synaptic transmission, cholinergic
B	0007584	biological_process	response to nutrient
B	0008753	molecular_function	NADPH dehydrogenase (quinone) activity
B	0009410	biological_process	response to xenobiotic stimulus
B	0009636	biological_process	response to toxic substance
B	0009725	biological_process	response to hormone
B	0009743	biological_process	response to carbohydrate
B	0010033	biological_process	response to organic substance
B	0014070	biological_process	response to organic cyclic compound
B	0014075	biological_process	response to amine
B	0016491	molecular_function	oxidoreductase activity
B	0019430	biological_process	removal of superoxide radicals
B	0030163	biological_process	protein catabolic process
B	0030425	cellular_component	dendrite
B	0032355	biological_process	response to estradiol
B	0032496	biological_process	response to lipopolysaccharide
B	0033574	biological_process	response to testosterone
B	0034599	biological_process	cellular response to oxidative stress
B	0042177	biological_process	negative regulation of protein catabolic process
B	0042360	biological_process	vitamin E metabolic process
B	0042373	biological_process	vitamin K metabolic process
B	0042802	molecular_function	identical protein binding
B	0043025	cellular_component	neuronal cell body
B	0043066	biological_process	negative regulation of apoptotic process
B	0043279	biological_process	response to alkaloid
B	0043525	biological_process	positive regulation of neuron apoptotic process
B	0045087	biological_process	innate immune response
B	0045202	cellular_component	synapse
B	0045454	biological_process	cell redox homeostasis
B	0045471	biological_process	response to ethanol
B	0050136	molecular_function	NADH:ubiquinone reductase (non-electrogenic) activity
B	0051602	biological_process	response to electrical stimulus
B	0070301	biological_process	cellular response to hydrogen peroxide
B	0070995	biological_process	NADPH oxidation
B	0071248	biological_process	cellular response to metal ion
B	1901698	biological_process	response to nitrogen compound
B	1904772	biological_process	response to tetrachloromethane
B	1904844	biological_process	response to L-glutamine
B	1904880	biological_process	response to hydrogen sulfide
B	1905395	biological_process	response to flavonoid
C	0000209	biological_process	protein polyubiquitination
C	0002931	biological_process	response to ischemia
C	0003723	molecular_function	RNA binding
C	0003955	molecular_function	NAD(P)H dehydrogenase (quinone) activity
C	0004128	molecular_function	cytochrome-b5 reductase activity, acting on NAD(P)H
C	0004784	molecular_function	superoxide dismutase activity
C	0005515	molecular_function	protein binding
C	0005634	cellular_component	nucleus
C	0005737	cellular_component	cytoplasm
C	0005829	cellular_component	cytosol
C	0006116	biological_process	NADH oxidation
C	0006743	biological_process	ubiquinone metabolic process
C	0006801	biological_process	superoxide metabolic process
C	0006805	biological_process	xenobiotic metabolic process
C	0006809	biological_process	nitric oxide biosynthetic process
C	0006979	biological_process	response to oxidative stress
C	0007271	biological_process	synaptic transmission, cholinergic
C	0007584	biological_process	response to nutrient
C	0008753	molecular_function	NADPH dehydrogenase (quinone) activity
C	0009410	biological_process	response to xenobiotic stimulus
C	0009636	biological_process	response to toxic substance
C	0009725	biological_process	response to hormone
C	0009743	biological_process	response to carbohydrate
C	0010033	biological_process	response to organic substance
C	0014070	biological_process	response to organic cyclic compound
C	0014075	biological_process	response to amine
C	0016491	molecular_function	oxidoreductase activity
C	0019430	biological_process	removal of superoxide radicals
C	0030163	biological_process	protein catabolic process
C	0030425	cellular_component	dendrite
C	0032355	biological_process	response to estradiol
C	0032496	biological_process	response to lipopolysaccharide
C	0033574	biological_process	response to testosterone
C	0034599	biological_process	cellular response to oxidative stress
C	0042177	biological_process	negative regulation of protein catabolic process
C	0042360	biological_process	vitamin E metabolic process
C	0042373	biological_process	vitamin K metabolic process
C	0042802	molecular_function	identical protein binding
C	0043025	cellular_component	neuronal cell body
C	0043066	biological_process	negative regulation of apoptotic process
C	0043279	biological_process	response to alkaloid
C	0043525	biological_process	positive regulation of neuron apoptotic process
C	0045087	biological_process	innate immune response
C	0045202	cellular_component	synapse
C	0045454	biological_process	cell redox homeostasis
C	0045471	biological_process	response to ethanol
C	0050136	molecular_function	NADH:ubiquinone reductase (non-electrogenic) activity
C	0051602	biological_process	response to electrical stimulus
C	0070301	biological_process	cellular response to hydrogen peroxide
C	0070995	biological_process	NADPH oxidation
C	0071248	biological_process	cellular response to metal ion
C	1901698	biological_process	response to nitrogen compound
C	1904772	biological_process	response to tetrachloromethane
C	1904844	biological_process	response to L-glutamine
C	1904880	biological_process	response to hydrogen sulfide
C	1905395	biological_process	response to flavonoid
D	0000209	biological_process	protein polyubiquitination
D	0002931	biological_process	response to ischemia
D	0003723	molecular_function	RNA binding
D	0003955	molecular_function	NAD(P)H dehydrogenase (quinone) activity
D	0004128	molecular_function	cytochrome-b5 reductase activity, acting on NAD(P)H
D	0004784	molecular_function	superoxide dismutase activity
D	0005515	molecular_function	protein binding
D	0005634	cellular_component	nucleus
D	0005737	cellular_component	cytoplasm
D	0005829	cellular_component	cytosol
D	0006116	biological_process	NADH oxidation
D	0006743	biological_process	ubiquinone metabolic process
D	0006801	biological_process	superoxide metabolic process
D	0006805	biological_process	xenobiotic metabolic process
D	0006809	biological_process	nitric oxide biosynthetic process
D	0006979	biological_process	response to oxidative stress
D	0007271	biological_process	synaptic transmission, cholinergic
D	0007584	biological_process	response to nutrient
D	0008753	molecular_function	NADPH dehydrogenase (quinone) activity
D	0009410	biological_process	response to xenobiotic stimulus
D	0009636	biological_process	response to toxic substance
D	0009725	biological_process	response to hormone
D	0009743	biological_process	response to carbohydrate
D	0010033	biological_process	response to organic substance
D	0014070	biological_process	response to organic cyclic compound
D	0014075	biological_process	response to amine
D	0016491	molecular_function	oxidoreductase activity
D	0019430	biological_process	removal of superoxide radicals
D	0030163	biological_process	protein catabolic process
D	0030425	cellular_component	dendrite
D	0032355	biological_process	response to estradiol
D	0032496	biological_process	response to lipopolysaccharide
D	0033574	biological_process	response to testosterone
D	0034599	biological_process	cellular response to oxidative stress
D	0042177	biological_process	negative regulation of protein catabolic process
D	0042360	biological_process	vitamin E metabolic process
D	0042373	biological_process	vitamin K metabolic process
D	0042802	molecular_function	identical protein binding
D	0043025	cellular_component	neuronal cell body
D	0043066	biological_process	negative regulation of apoptotic process
D	0043279	biological_process	response to alkaloid
D	0043525	biological_process	positive regulation of neuron apoptotic process
D	0045087	biological_process	innate immune response
D	0045202	cellular_component	synapse
D	0045454	biological_process	cell redox homeostasis
D	0045471	biological_process	response to ethanol
D	0050136	molecular_function	NADH:ubiquinone reductase (non-electrogenic) activity
D	0051602	biological_process	response to electrical stimulus
D	0070301	biological_process	cellular response to hydrogen peroxide
D	0070995	biological_process	NADPH oxidation
D	0071248	biological_process	cellular response to metal ion
D	1901698	biological_process	response to nitrogen compound
D	1904772	biological_process	response to tetrachloromethane
D	1904844	biological_process	response to L-glutamine
D	1904880	biological_process	response to hydrogen sulfide
D	1905395	biological_process	response to flavonoid

Functional Information from PDB Data

site_id	AC1
Number of Residues	22
Details	BINDING SITE FOR RESIDUE FAD A 601

Chain	Residue
A	HIS11
A	TRP105
A	PHE106
A	THR147
A	THR148
A	GLY149
A	GLY150
A	TYR155
A	ILE192
A	ARG200
A	LEU204
A	THR15
C	GLN66
C	TYR67
C	E09701
A	SER16
A	PHE17
A	ASN18
A	ALA20
A	PRO102
A	LEU103
A	GLN104

---

site_id	AC2
Number of Residues	22
Details	BINDING SITE FOR RESIDUE FAD B 602

Chain	Residue
B	HIS11
B	THR15
B	SER16
B	PHE17
B	ASN18
B	ALA20
B	PRO102
B	LEU103
B	GLN104
B	TRP105
B	PHE106
B	THR147
B	THR148
B	GLY149
B	GLY150
B	TYR155
B	ILE192
B	ARG200
B	LEU204
D	GLN66
D	TYR67
D	E09702

---

site_id	AC3
Number of Residues	21
Details	BINDING SITE FOR RESIDUE FAD C 603

Chain	Residue
A	GLN66
A	TYR67
A	E09703
C	HIS11
C	THR15
C	SER16
C	PHE17
C	ASN18
C	ALA20
C	PRO102
C	LEU103
C	GLN104
C	TRP105
C	PHE106
C	THR147
C	THR148
C	GLY149
C	GLY150
C	TYR155
C	ILE192
C	ARG200

---

site_id	AC4
Number of Residues	23
Details	BINDING SITE FOR RESIDUE FAD D 604

Chain	Residue
B	GLN66
B	TYR67
B	PRO68
B	E09704
B	HOH716
D	HIS11
D	THR15
D	SER16
D	PHE17
D	ASN18
D	ALA20
D	PRO102
D	LEU103
D	GLN104
D	TRP105
D	PHE106
D	THR147
D	THR148
D	GLY149
D	GLY150
D	TYR155
D	ILE192
D	ARG200

---

site_id	AC5
Number of Residues	11
Details	BINDING SITE FOR RESIDUE E09 C 701

Chain	Residue
A	TRP105
A	PHE106
A	GLY149
A	GLY150
A	HIS161
A	FAD601
C	PRO68
C	TYR126
C	TYR128
C	GLY174
C	PHE178

---

site_id	AC6
Number of Residues	10
Details	BINDING SITE FOR RESIDUE E09 D 702

Chain	Residue
B	TRP105
B	PHE106
B	GLY149
B	GLY150
B	HIS161
B	FAD602
D	PRO68
D	TYR126
D	TYR128
D	PHE178

---

site_id	AC7
Number of Residues	10
Details	BINDING SITE FOR RESIDUE E09 A 703

Chain	Residue
A	PRO68
A	TYR126
A	TYR128
A	GLY174
A	PHE178
C	PHE106
C	GLY149
C	GLY150
C	HIS161
C	FAD603

---

site_id	AC8
Number of Residues	10
Details	BINDING SITE FOR RESIDUE E09 B 704

Chain	Residue
B	PRO68
B	TYR126
B	TYR128
B	GLY174
B	PHE178
D	PHE106
D	GLY149
D	GLY150
D	HIS161
D	FAD604

---

Functional Information from SwissProt/UniProt

site_id	SWS_FT_FI1
Number of Residues	28
Details	BINDING: BINDING => ECO:0000269|PubMed:10543876, ECO:0000269|PubMed:10706635, ECO:0000269|PubMed:11735396

Chain	Residue	Details
A	HIS11
B	GLN66
B	LEU103
B	THR147
B	TYR155
B	ARG200
C	HIS11
C	PHE17
C	GLN66
C	LEU103
C	THR147
A	PHE17
C	TYR155
C	ARG200
D	HIS11
D	PHE17
D	GLN66
D	LEU103
D	THR147
D	TYR155
D	ARG200
A	GLN66
A	LEU103
A	THR147
A	TYR155
A	ARG200
B	HIS11
B	PHE17

---

site_id	SWS_FT_FI2
Number of Residues	4
Details	BINDING:

Chain	Residue	Details
A	ALA125
B	ALA125
C	ALA125
D	ALA125

---

site_id	SWS_FT_FI3
Number of Residues	4
Details	MOD_RES: Phosphoserine => ECO:0007744|PubMed:23186163

Chain	Residue	Details
A	SER81
B	SER81
C	SER81
D	SER81

---

site_id	SWS_FT_FI4
Number of Residues	12
Details	CROSSLNK: Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) => ECO:0007744|PubMed:28112733

Chain	Residue	Details
A	LYS249
D	LYS249
D	LYS250
A	LYS250
B	LYS249
B	LYS250
C	LYS249
C	LYS250

---

Catalytic Information from CSA

site_id	MCSA1
Number of Residues	3
Details	M-CSA 3

Chain	Residue	Details
A	GLY149	electrostatic stabiliser, hydrogen bond donor
A	TYR155	electrostatic stabiliser, hydrogen bond acceptor, hydrogen bond donor, proton acceptor, proton donor, proton relay
A	HIS161	hydrogen bond acceptor, hydrogen bond donor, proton acceptor, proton donor, proton relay

---

site_id	MCSA2
Number of Residues	3
Details	M-CSA 3

Chain	Residue	Details
B	GLY149	electrostatic stabiliser, hydrogen bond donor
B	TYR155	electrostatic stabiliser, hydrogen bond acceptor, hydrogen bond donor, proton acceptor, proton donor, proton relay
B	HIS161	hydrogen bond acceptor, hydrogen bond donor, proton acceptor, proton donor, proton relay

---

site_id	MCSA3
Number of Residues	3
Details	M-CSA 3

Chain	Residue	Details
C	GLY149	electrostatic stabiliser, hydrogen bond donor
C	TYR155	electrostatic stabiliser, hydrogen bond acceptor, hydrogen bond donor, proton acceptor, proton donor, proton relay
C	HIS161	hydrogen bond acceptor, hydrogen bond donor, proton acceptor, proton donor, proton relay

---

site_id	MCSA4
Number of Residues	3
Details	M-CSA 3

Chain	Residue	Details
D	GLY149	electrostatic stabiliser, hydrogen bond donor
D	TYR155	electrostatic stabiliser, hydrogen bond acceptor, hydrogen bond donor, proton acceptor, proton donor, proton relay
D	HIS161	hydrogen bond acceptor, hydrogen bond donor, proton acceptor, proton donor, proton relay

---