3CCZ
Thermodynamic and structure guided design of statin 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 1 |
| Chain | Residue |
| A | ALA654 |
| A | MET655 |
| A | GLY656 |
| A | MET657 |
| A | ASN658 |
| A | HOH885 |
| A | HOH975 |
| A | HOH982 |
| A | HOH1128 |
| site_id | AC2 |
| Number of Residues | 6 |
| Details | BINDING SITE FOR RESIDUE SO4 B 2 |
| Chain | Residue |
| B | ALA654 |
| B | GLY656 |
| B | MET657 |
| B | ASN658 |
| B | HOH904 |
| B | HOH940 |
| site_id | AC3 |
| Number of Residues | 9 |
| Details | BINDING SITE FOR RESIDUE SO4 C 3 |
| Chain | Residue |
| C | ALA654 |
| C | MET655 |
| C | GLY656 |
| C | MET657 |
| C | ASN658 |
| C | HOH882 |
| C | HOH936 |
| C | HOH1134 |
| C | HOH1141 |
| site_id | AC4 |
| Number of Residues | 7 |
| Details | BINDING SITE FOR RESIDUE SO4 D 4 |
| Chain | Residue |
| D | ALA654 |
| D | MET655 |
| D | GLY656 |
| D | MET657 |
| D | ASN658 |
| D | HOH891 |
| D | HOH929 |
| site_id | AC5 |
| Number of Residues | 19 |
| Details | BINDING SITE FOR RESIDUE 5HI A 876 |
| Chain | Residue |
| A | ARG590 |
| A | SER661 |
| A | SER684 |
| A | ASP690 |
| A | LYS691 |
| A | LYS692 |
| A | HOH878 |
| A | HOH1197 |
| A | HOH1200 |
| B | GLU559 |
| B | CYS561 |
| B | SER565 |
| B | LYS735 |
| B | ALA751 |
| B | HIS752 |
| B | ASN755 |
| B | LEU853 |
| B | ALA856 |
| B | HOH1021 |
| site_id | AC6 |
| Number of Residues | 15 |
| Details | BINDING SITE FOR RESIDUE 5HI B 876 |
| Chain | Residue |
| A | GLU559 |
| A | CYS561 |
| A | SER565 |
| A | LYS735 |
| A | ALA751 |
| A | ASN755 |
| A | LEU853 |
| B | ARG590 |
| B | SER661 |
| B | SER684 |
| B | ASN686 |
| B | ASP690 |
| B | LYS691 |
| B | LYS692 |
| B | HOH878 |
| site_id | AC7 |
| Number of Residues | 17 |
| Details | BINDING SITE FOR RESIDUE 5HI C 876 |
| Chain | Residue |
| C | ARG590 |
| C | SER661 |
| C | SER684 |
| C | ASP690 |
| C | LYS691 |
| C | LYS692 |
| C | HOH888 |
| C | HOH1066 |
| C | HOH1155 |
| D | GLU559 |
| D | CYS561 |
| D | SER565 |
| D | LYS735 |
| D | ALA751 |
| D | HIS752 |
| D | ASN755 |
| D | LEU853 |
| site_id | AC8 |
| Number of Residues | 18 |
| Details | BINDING SITE FOR RESIDUE 5HI D 876 |
| Chain | Residue |
| D | HOH1158 |
| C | GLU559 |
| C | CYS561 |
| C | SER565 |
| C | ARG568 |
| C | LYS735 |
| C | ALA751 |
| C | HIS752 |
| C | ASN755 |
| C | LEU853 |
| D | ARG590 |
| D | SER661 |
| D | SER684 |
| D | ASP690 |
| D | LYS691 |
| D | LYS692 |
| D | HOH877 |
| D | HOH1142 |
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 | |
| A | LYS691 | |
| A | ASP767 | |
| B | GLU559 | |
| B | LYS691 | |
| B | ASP767 | |
| C | GLU559 | |
| C | LYS691 | |
| C | ASP767 | |
| D | GLU559 | |
| D | LYS691 | |
| D | 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 | SER865 | |
| A | ASN870 | |
| B | SER565 | |
| B | SER626 | |
| B | ASP653 | |
| B | VAL720 | |
| B | SER865 | |
| B | ASN870 | |
| C | SER565 | |
| C | SER626 | |
| C | ASP653 | |
| C | VAL720 | |
| C | SER865 | |
| C | ASN870 | |
| D | SER565 | |
| D | SER626 | |
| D | ASP653 | |
| D | VAL720 | |
| D | SER865 | |
| D | ASN870 | |
| A | SER565 | |
| A | SER626 | |
| A | ASP653 | |
| A | VAL720 |
| 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 | 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 |
