2Q6B
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 | 5 |
| Details | BINDING SITE FOR RESIDUE SO4 A 2001 |
| Chain | Residue |
| A | GLY656 |
| A | MET657 |
| A | ASN658 |
| A | HOH3109 |
| A | HOH3137 |
| site_id | AC2 |
| Number of Residues | 6 |
| Details | BINDING SITE FOR RESIDUE SO4 B 2002 |
| Chain | Residue |
| B | HOH2028 |
| B | HOH2101 |
| B | ALA654 |
| B | GLY656 |
| B | MET657 |
| B | ASN658 |
| site_id | AC3 |
| Number of Residues | 7 |
| Details | BINDING SITE FOR RESIDUE SO4 C 2003 |
| Chain | Residue |
| C | ALA654 |
| C | GLY656 |
| C | MET657 |
| C | ASN658 |
| C | HOH3039 |
| C | HOH3062 |
| C | HOH3231 |
| 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 | HOH3058 |
| D | HOH3203 |
| D | HOH3287 |
| site_id | AC5 |
| Number of Residues | 21 |
| Details | BINDING SITE FOR RESIDUE HR2 A 3001 |
| Chain | Residue |
| A | ARG590 |
| A | SER661 |
| A | VAL683 |
| A | SER684 |
| A | ASP690 |
| A | LYS691 |
| A | LYS692 |
| A | HOH3003 |
| B | GLU559 |
| B | GLY560 |
| B | CYS561 |
| B | LEU562 |
| B | SER565 |
| B | ARG568 |
| B | LYS735 |
| B | ALA751 |
| B | HIS752 |
| B | ASN755 |
| B | LEU853 |
| B | HIS861 |
| B | LEU862 |
| site_id | AC6 |
| Number of Residues | 22 |
| Details | BINDING SITE FOR RESIDUE HR2 A 3002 |
| Chain | Residue |
| A | GLU559 |
| A | GLY560 |
| A | CYS561 |
| A | LEU562 |
| A | SER565 |
| A | ARG568 |
| A | LYS735 |
| A | ALA751 |
| A | ASN755 |
| A | LEU853 |
| A | HIS861 |
| A | LYS864 |
| A | HOH3012 |
| B | ARG590 |
| B | MET657 |
| B | SER661 |
| B | VAL683 |
| B | SER684 |
| B | ASN686 |
| B | ASP690 |
| B | LYS691 |
| B | LYS692 |
| site_id | AC7 |
| Number of Residues | 22 |
| Details | BINDING SITE FOR RESIDUE HR2 C 3003 |
| Chain | Residue |
| C | GLU559 |
| C | GLY560 |
| C | CYS561 |
| C | LEU562 |
| C | SER565 |
| C | ARG568 |
| C | LYS735 |
| C | ALA751 |
| C | HIS752 |
| C | ASN755 |
| C | LEU853 |
| C | HIS861 |
| C | VAL863 |
| C | HOH3008 |
| D | ARG590 |
| D | SER661 |
| D | VAL683 |
| D | SER684 |
| D | ASN686 |
| D | ASP690 |
| D | LYS691 |
| D | LYS692 |
| site_id | AC8 |
| Number of Residues | 21 |
| Details | BINDING SITE FOR RESIDUE HR2 D 3004 |
| Chain | Residue |
| D | GLU559 |
| D | GLY560 |
| D | CYS561 |
| D | LEU562 |
| D | SER565 |
| D | ARG568 |
| D | LYS735 |
| D | ALA751 |
| D | HIS752 |
| D | ASN755 |
| D | LEU853 |
| D | HIS861 |
| D | HOH3012 |
| C | ARG590 |
| C | SER661 |
| C | VAL683 |
| C | SER684 |
| C | ASN686 |
| C | ASP690 |
| C | LYS691 |
| C | LYS692 |
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 | CSA2 |
| Number of Residues | 2 |
| Details | Annotated By Reference To The Literature 1dqa |
| Chain | Residue | Details |
| D | GLU559 | |
| D | HIS866 |
| 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 |
