Summary Structural details Experimental details Functional details Sequence Neighbor History Downloads

2Q6C

Design and synthesis of novel, conformationally restricted HMG-COA reductase inhibitors

Functional Information from GO Data

Chain	GOid	namespace	contents
A	0004420	molecular_function	hydroxymethylglutaryl-CoA reductase (NADPH) activity
A	0005789	cellular_component	endoplasmic reticulum membrane
A	0008299	biological_process	isoprenoid biosynthetic process
A	0015936	biological_process	coenzyme A metabolic process
A	0016616	molecular_function	oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor
A	0050661	molecular_function	NADP binding
B	0004420	molecular_function	hydroxymethylglutaryl-CoA reductase (NADPH) activity
B	0005789	cellular_component	endoplasmic reticulum membrane
B	0008299	biological_process	isoprenoid biosynthetic process
B	0015936	biological_process	coenzyme A metabolic process
B	0016616	molecular_function	oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor
B	0050661	molecular_function	NADP binding
C	0004420	molecular_function	hydroxymethylglutaryl-CoA reductase (NADPH) activity
C	0005789	cellular_component	endoplasmic reticulum membrane
C	0008299	biological_process	isoprenoid biosynthetic process
C	0015936	biological_process	coenzyme A metabolic process
C	0016616	molecular_function	oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor
C	0050661	molecular_function	NADP binding
D	0004420	molecular_function	hydroxymethylglutaryl-CoA reductase (NADPH) activity
D	0005789	cellular_component	endoplasmic reticulum membrane
D	0008299	biological_process	isoprenoid biosynthetic process
D	0015936	biological_process	coenzyme A metabolic process
D	0016616	molecular_function	oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor
D	0050661	molecular_function	NADP binding

Functional Information from PDB Data

site_id	AC1
Number of Residues	9
Details	BINDING SITE FOR RESIDUE SO4 A 2001

Chain	Residue
A	ALA654
A	MET655
A	GLY656
A	MET657
A	ASN658
A	HOH3023
A	HOH3047
A	HOH3098
A	HOH3112

site_id	AC2
Number of Residues	7
Details	BINDING SITE FOR RESIDUE SO4 B 2002

Chain	Residue
B	ALA654
B	MET655
B	GLY656
B	MET657
B	ASN658
B	HOH3041
B	HOH3046

site_id	AC3
Number of Residues	9
Details	BINDING SITE FOR RESIDUE SO4 C 2003

Chain	Residue
C	ALA654
C	MET655
C	GLY656
C	MET657
C	ASN658
C	HOH3012
C	HOH3058
C	HOH3138
C	HOH3216

site_id	AC4
Number of Residues	8
Details	BINDING SITE FOR RESIDUE SO4 D 2004

Chain	Residue
D	ALA654
D	MET655
D	GLY656
D	MET657
D	ASN658
D	HOH3024
D	HOH3062
D	HOH3188

site_id	AC5
Number of Residues	20
Details	BINDING SITE FOR RESIDUE HR1 B 3001

Chain	Residue
A	GLU559
A	GLY560
A	CYS561
A	SER565
A	ARG568
A	LYS735
A	ALA751
A	ASN755
A	ALA856
A	HIS861
B	ARG590
B	SER661
B	VAL683
B	SER684
B	ASN686
B	ASP690
B	LYS691
B	LYS692
B	HOH3008
B	HOH3154

site_id	AC6
Number of Residues	18
Details	BINDING SITE FOR RESIDUE HR1 A 3002

Chain	Residue
A	ARG590
A	SER661
A	VAL683
A	SER684
A	ASN686
A	ASP690
A	LYS691
A	LYS692
A	HOH3004
A	HOH3147
B	GLU559
B	GLY560
B	CYS561
B	SER565
B	LYS735
B	ALA751
B	ASN755
B	LEU853

site_id	AC7
Number of Residues	18
Details	BINDING SITE FOR RESIDUE HR1 D 3003

Chain	Residue
C	GLU559
C	CYS561
C	ARG568
C	LYS735
C	ALA751
C	HIS752
C	ASN755
C	LEU853
C	HOH3114
D	ARG590
D	MET657
D	VAL683
D	SER684
D	ASP690
D	LYS691
D	LYS692
D	HOH3011
D	HOH3191

site_id	AC8
Number of Residues	16
Details	BINDING SITE FOR RESIDUE HR1 C 3004

Chain	Residue
D	LYS735
D	ALA751
D	HIS752
D	ASN755
D	LEU853
D	HIS861
C	ARG590
C	VAL683
C	SER684
C	ASP690
C	LYS691
C	LYS692
C	HOH3194
C	HOH3279
D	GLU559
D	CYS561

Functional Information from PROSITE/UniProt

site_id	PS00066
Number of Residues	15
Details	HMG_COA_REDUCTASE_1 Hydroxymethylglutaryl-coenzyme A reductases signature 1. RfQSrSGDaMGmNmI

Chain	Residue	Details
A	ARG646-ILE660

site_id	PS00318
Number of Residues	8
Details	HMG_COA_REDUCTASE_2 Hydroxymethylglutaryl-coenzyme A reductases signature 2. IGtVGGGT

Chain	Residue	Details
A	ILE802-THR809

site_id	PS01192
Number of Residues	14
Details	HMG_COA_REDUCTASE_3 Hydroxymethylglutaryl-coenzyme A reductases signature 3. ALaAghLvKSHMiH

Chain	Residue	Details
A	ALA856-HIS869

Functional Information from SwissProt/UniProt

site_id	SWS_FT_FI1
Number of Residues	12
Details	ACT_SITE: Charge relay system => ECO:0000303\|PubMed:10698924, ECO:0000303\|PubMed:11349148

Chain	Residue	Details
A	GLU559
D	GLU559
D	LYS691
D	ASP767
A	LYS691
A	ASP767
B	GLU559
B	LYS691
B	ASP767
C	GLU559
C	LYS691
C	ASP767

site_id	SWS_FT_FI2
Number of Residues	4
Details	ACT_SITE: Proton donor => ECO:0000255\|PROSITE-ProRule:PRU10003

Chain	Residue	Details
A	HIS866
B	HIS866
C	HIS866
D	HIS866

site_id	SWS_FT_FI3
Number of Residues	24
Details	BINDING: BINDING => ECO:0000269\|PubMed:11349148, ECO:0007744\|PDB:1DQA

Chain	Residue	Details
A	SER565
B	VAL720
B	SER865
B	ASN870
C	SER565
C	SER626
C	ASP653
C	VAL720
C	SER865
C	ASN870
D	SER565
A	SER626
D	SER626
D	ASP653
D	VAL720
D	SER865
D	ASN870
A	ASP653
A	VAL720
A	SER865
A	ASN870
B	SER565
B	SER626
B	ASP653

site_id	SWS_FT_FI4
Number of Residues	4
Details	MOD_RES: Phosphoserine => ECO:0007744\|PubMed:23186163

Chain	Residue	Details
A	SER504
B	SER504
C	SER504
D	SER504

site_id	SWS_FT_FI5
Number of Residues	4
Details	MOD_RES: Phosphoserine => ECO:0000250\|UniProtKB:P00347, ECO:0007744\|PubMed:24275569

Chain	Residue	Details
A	SER872
B	SER872
C	SER872
D	SER872

Catalytic Information from CSA

site_id	CSA1
Number of Residues	12
Details	Annotated By Reference To The Literature 1dqa

Chain	Residue	Details
A	LYS691
B	LYS691
B	ASP767
B	GLU559
A	ASP767
A	GLU559
D	LYS691
D	ASP767
D	GLU559
C	LYS691
C	ASP767
C	GLU559

site_id	MCSA1
Number of Residues	4
Details	M-CSA 93

Chain	Residue	Details
A	GLU559	electrostatic stabiliser, hydrogen bond acceptor, hydrogen bond donor, proton acceptor, proton donor
A	LYS691	electrostatic stabiliser, hydrogen bond donor, proton acceptor, proton donor
A	ASP767	activator, electrostatic stabiliser, hydrogen bond acceptor
A	HIS866	hydrogen bond acceptor, hydrogen bond donor, proton acceptor, proton donor

site_id	MCSA2
Number of Residues	4
Details	M-CSA 93

Chain	Residue	Details
B	GLU559	electrostatic stabiliser, hydrogen bond acceptor, hydrogen bond donor, proton acceptor, proton donor
B	LYS691	electrostatic stabiliser, hydrogen bond donor, proton acceptor, proton donor
B	ASP767	activator, electrostatic stabiliser, hydrogen bond acceptor
B	HIS866	hydrogen bond acceptor, hydrogen bond donor, proton acceptor, proton donor

site_id	MCSA3
Number of Residues	4
Details	M-CSA 93

Chain	Residue	Details
C	GLU559	electrostatic stabiliser, hydrogen bond acceptor, hydrogen bond donor, proton acceptor, proton donor
C	LYS691	electrostatic stabiliser, hydrogen bond donor, proton acceptor, proton donor
C	ASP767	activator, electrostatic stabiliser, hydrogen bond acceptor
C	HIS866	hydrogen bond acceptor, hydrogen bond donor, proton acceptor, proton donor

site_id	MCSA4
Number of Residues	4
Details	M-CSA 93

Chain	Residue	Details
D	GLU559	electrostatic stabiliser, hydrogen bond acceptor, hydrogen bond donor, proton acceptor, proton donor
D	LYS691	electrostatic stabiliser, hydrogen bond donor, proton acceptor, proton donor
D	ASP767	activator, electrostatic stabiliser, hydrogen bond acceptor
D	HIS866	hydrogen bond acceptor, hydrogen bond donor, proton acceptor, proton donor

		Sequence (fasta)
		PDBx/mmCIF
		PDBML format (no-atom)
		PDB format (full)
		Validation report (PDF)
		EDMap 2fo-fc (MTZ)