3H4G

Structure of aldehyde reductase holoenzyme in complex with potent aldose reductase inhibitor Fidarestat: Implications for inhibitor binding and selectivity

Replaces:  2AO0

Functional Information from GO Data

Chain	GOid	namespace	contents
A	0004032	molecular_function	aldose reductase (NADPH) activity
A	0004745	molecular_function	all-trans-retinol dehydrogenase (NAD+) activity
A	0005737	cellular_component	cytoplasm
A	0005829	cellular_component	cytosol
A	0005886	cellular_component	plasma membrane
A	0006629	biological_process	lipid metabolic process
A	0008106	molecular_function	alcohol dehydrogenase (NADP+) activity
A	0016324	cellular_component	apical plasma membrane
A	0016491	molecular_function	oxidoreductase activity
A	0019853	biological_process	L-ascorbic acid biosynthetic process
A	0042840	biological_process	D-glucuronate catabolic process
A	0046185	biological_process	aldehyde catabolic process
A	0047655	molecular_function	allyl-alcohol dehydrogenase activity
A	0047939	molecular_function	L-glucuronate reductase activity
A	0047941	molecular_function	glucuronolactone reductase activity
A	0047956	molecular_function	glycerol dehydrogenase (NADP+) activity
A	0110095	biological_process	cellular detoxification of aldehyde
A	0160163	molecular_function	S-nitrosoglutathione reductase (NADPH) activity
A	1990002	molecular_function	methylglyoxal reductase (NADPH) (acetol producing) activity

Functional Information from PDB Data

site_id	AC1
Number of Residues	3
Details	BINDING SITE FOR RESIDUE SO4 A 361

Chain	Residue
A	ARG251
A	PHE277
A	HOH2150

---

site_id	AC2
Number of Residues	36
Details	BINDING SITE FOR RESIDUE NAP A 2350

Chain	Residue
A	HIS113
A	SER162
A	ASN163
A	GLN184
A	TYR210
A	SER211
A	PRO212
A	LEU213
A	GLY214
A	SER215
A	ASP217
A	ALA246
A	ILE261
A	PRO262
A	LYS263
A	SER264
A	VAL265
A	THR266
A	ARG269
A	GLN272
A	ASN273
A	HOH2011
A	HOH2046
A	HOH2052
A	HOH2062
A	HOH2170
A	HOH2201
A	HOH2201
A	HOH2249
A	FID2401
A	GLY20
A	THR21
A	TRP22
A	ASP45
A	TYR50
A	LYS80

---

site_id	AC3
Number of Residues	11
Details	BINDING SITE FOR RESIDUE FID A 2401

Chain	Residue
A	TRP22
A	ILE49
A	TYR50
A	HIS113
A	TRP114
A	TRP220
A	ILE299
A	VAL300
A	PRO301
A	HOH2275
A	NAP2350

---

Functional Information from PROSITE/UniProt

site_id	PS00062
Number of Residues	18
Details	ALDOKETO_REDUCTASE_2 Aldo/keto reductase family signature 2. LealvakglVRALGLSNF

Chain	Residue	Details
A	LEU147-PHE164

---

site_id	PS00063
Number of Residues	16
Details	ALDOKETO_REDUCTASE_3 Aldo/keto reductase family putative active site signature. IPKSVTpsRIlQNiQV

Chain	Residue	Details
A	ILE261-VAL276

---

site_id	PS00798
Number of Residues	18
Details	ALDOKETO_REDUCTASE_1 Aldo/keto reductase family signature 1. GYRHIDCAaiygnEleIG

Chain	Residue	Details
A	GLY40-GLY57

---

Functional Information from SwissProt/UniProt

site_id	SWS_FT_FI1
Number of Residues	1
Details	ACT_SITE: Proton donor => ECO:0000269|PubMed:11306083, ECO:0000269|PubMed:7552731

Chain	Residue	Details
A	TYR50

---

site_id	SWS_FT_FI2
Number of Residues	1
Details	BINDING: BINDING => ECO:0000250|UniProtKB:O60218

Chain	Residue	Details
A	GLY11

---

site_id	SWS_FT_FI3
Number of Residues	15
Details	BINDING: BINDING => ECO:0000269|PubMed:11306083, ECO:0007744|PDB:1HQT

Chain	Residue	Details
A	THR21
A	LYS263
A	SER264
A	VAL265
A	THR266
A	ARG269
A	ASN273
A	TRP22
A	ASP45
A	SER162
A	ASN163
A	SER211
A	LEU213
A	SER215
A	SER216

---

site_id	SWS_FT_FI4
Number of Residues	1
Details	BINDING: BINDING => ECO:0000269|PubMed:11306083, ECO:0007744|PDB:3CV7

Chain	Residue	Details
A	GLN272

---

site_id	SWS_FT_FI5
Number of Residues	1
Details	SITE: Lowers pKa of active site Tyr => ECO:0000250|UniProtKB:P14550

Chain	Residue	Details
A	LYS80

---

site_id	SWS_FT_FI6
Number of Residues	1
Details	MOD_RES: N-acetylalanine => ECO:0000250|UniProtKB:P14550

Chain	Residue	Details
A	ALA2

---

site_id	SWS_FT_FI7
Number of Residues	1
Details	MOD_RES: Phosphoserine => ECO:0000250|UniProtKB:P51635

Chain	Residue	Details
A	SER4

---

site_id	SWS_FT_FI8
Number of Residues	1
Details	MOD_RES: N6-succinyllysine; alternate => ECO:0000250|UniProtKB:Q9JII6

Chain	Residue	Details
A	LYS127

---

site_id	SWS_FT_FI9
Number of Residues	1
Details	MOD_RES: N6-succinyllysine => ECO:0000250|UniProtKB:Q9JII6

Chain	Residue	Details
A	LYS145

---

site_id	SWS_FT_FI10
Number of Residues	1
Details	MOD_RES: Phosphoserine => ECO:0000250|UniProtKB:P14550

Chain	Residue	Details
A	SER211

---

Catalytic Information from CSA

site_id	CSA1
Number of Residues	4
Details	Annotated By Reference To The Literature 1mrq

Chain	Residue	Details
A	LYS80
A	HIS113
A	ASP45
A	TYR50

---

site_id	CSA2
Number of Residues	2
Details	Annotated By Reference To The Literature 1mrq

Chain	Residue	Details
A	LYS80
A	TYR50

---