1PJ3
Crystal structure of human mitochondrial NAD(P)+-dependent malic enzyme in a pentary complex with natural substrate pyruvate, cofactor NAD+, Mn++, and allosteric activator fumarate.
Functional Information from GO Data
| Chain | GOid | namespace | contents |
| A | 0004470 | molecular_function | malic enzyme activity |
| A | 0004471 | molecular_function | malate dehydrogenase (decarboxylating) (NAD+) activity |
| A | 0004473 | molecular_function | malate dehydrogenase (decarboxylating) (NADP+) activity |
| A | 0005739 | cellular_component | mitochondrion |
| A | 0005759 | cellular_component | mitochondrial matrix |
| A | 0006090 | biological_process | pyruvate metabolic process |
| A | 0006108 | biological_process | malate metabolic process |
| A | 0008948 | molecular_function | oxaloacetate decarboxylase activity |
| A | 0009055 | molecular_function | electron transfer activity |
| A | 0016491 | molecular_function | oxidoreductase activity |
| A | 0016616 | molecular_function | oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor |
| A | 0043231 | cellular_component | intracellular membrane-bounded organelle |
| A | 0046872 | molecular_function | metal ion binding |
| A | 0051287 | molecular_function | NAD binding |
| A | 1902031 | biological_process | regulation of NADP metabolic process |
| B | 0004470 | molecular_function | malic enzyme activity |
| B | 0004471 | molecular_function | malate dehydrogenase (decarboxylating) (NAD+) activity |
| B | 0004473 | molecular_function | malate dehydrogenase (decarboxylating) (NADP+) activity |
| B | 0005739 | cellular_component | mitochondrion |
| B | 0005759 | cellular_component | mitochondrial matrix |
| B | 0006090 | biological_process | pyruvate metabolic process |
| B | 0006108 | biological_process | malate metabolic process |
| B | 0008948 | molecular_function | oxaloacetate decarboxylase activity |
| B | 0009055 | molecular_function | electron transfer activity |
| B | 0016491 | molecular_function | oxidoreductase activity |
| B | 0016616 | molecular_function | oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor |
| B | 0043231 | cellular_component | intracellular membrane-bounded organelle |
| B | 0046872 | molecular_function | metal ion binding |
| B | 0051287 | molecular_function | NAD binding |
| B | 1902031 | biological_process | regulation of NADP metabolic process |
| C | 0004470 | molecular_function | malic enzyme activity |
| C | 0004471 | molecular_function | malate dehydrogenase (decarboxylating) (NAD+) activity |
| C | 0004473 | molecular_function | malate dehydrogenase (decarboxylating) (NADP+) activity |
| C | 0005739 | cellular_component | mitochondrion |
| C | 0005759 | cellular_component | mitochondrial matrix |
| C | 0006090 | biological_process | pyruvate metabolic process |
| C | 0006108 | biological_process | malate metabolic process |
| C | 0008948 | molecular_function | oxaloacetate decarboxylase activity |
| C | 0009055 | molecular_function | electron transfer activity |
| C | 0016491 | molecular_function | oxidoreductase activity |
| C | 0016616 | molecular_function | oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor |
| C | 0043231 | cellular_component | intracellular membrane-bounded organelle |
| C | 0046872 | molecular_function | metal ion binding |
| C | 0051287 | molecular_function | NAD binding |
| C | 1902031 | biological_process | regulation of NADP metabolic process |
| D | 0004470 | molecular_function | malic enzyme activity |
| D | 0004471 | molecular_function | malate dehydrogenase (decarboxylating) (NAD+) activity |
| D | 0004473 | molecular_function | malate dehydrogenase (decarboxylating) (NADP+) activity |
| D | 0005739 | cellular_component | mitochondrion |
| D | 0005759 | cellular_component | mitochondrial matrix |
| D | 0006090 | biological_process | pyruvate metabolic process |
| D | 0006108 | biological_process | malate metabolic process |
| D | 0008948 | molecular_function | oxaloacetate decarboxylase activity |
| D | 0009055 | molecular_function | electron transfer activity |
| D | 0016491 | molecular_function | oxidoreductase activity |
| D | 0016616 | molecular_function | oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor |
| D | 0043231 | cellular_component | intracellular membrane-bounded organelle |
| D | 0046872 | molecular_function | metal ion binding |
| D | 0051287 | molecular_function | NAD binding |
| D | 1902031 | biological_process | regulation of NADP metabolic process |
Functional Information from PDB Data
| site_id | AC1 |
| Number of Residues | 5 |
| Details | BINDING SITE FOR RESIDUE MN A 604 |
| Chain | Residue |
| A | GLU255 |
| A | ASP256 |
| A | ASP279 |
| A | PYR603 |
| A | HOH4903 |
| site_id | AC2 |
| Number of Residues | 6 |
| Details | BINDING SITE FOR RESIDUE MN B 1604 |
| Chain | Residue |
| B | PYR1603 |
| B | HOH4902 |
| B | ARG1165 |
| B | GLU1255 |
| B | ASP1256 |
| B | ASP1279 |
| site_id | AC3 |
| Number of Residues | 6 |
| Details | BINDING SITE FOR RESIDUE MN C 2604 |
| Chain | Residue |
| C | ARG2165 |
| C | GLU2255 |
| C | ASP2256 |
| C | ASP2279 |
| C | PYR2603 |
| C | HOH4904 |
| site_id | AC4 |
| Number of Residues | 6 |
| Details | BINDING SITE FOR RESIDUE MN D 3604 |
| Chain | Residue |
| D | ARG3165 |
| D | GLU3255 |
| D | ASP3256 |
| D | ASP3279 |
| D | PYR3603 |
| D | HOH4001 |
| site_id | AC5 |
| Number of Residues | 13 |
| Details | BINDING SITE FOR RESIDUE PYR A 603 |
| Chain | Residue |
| A | TYR112 |
| A | ARG165 |
| A | LEU167 |
| A | LYS183 |
| A | GLU255 |
| A | ASP256 |
| A | ASP279 |
| A | ASN421 |
| A | ASN466 |
| A | ASN467 |
| A | NAD601 |
| A | MN604 |
| A | HOH5000 |
| site_id | AC6 |
| Number of Residues | 14 |
| Details | BINDING SITE FOR RESIDUE PYR B 1603 |
| Chain | Residue |
| B | TYR1112 |
| B | ARG1165 |
| B | LEU1167 |
| B | LYS1183 |
| B | GLU1255 |
| B | ASP1256 |
| B | ASP1279 |
| B | ASN1421 |
| B | ASN1466 |
| B | ASN1467 |
| B | NAD1601 |
| B | MN1604 |
| B | HOH4902 |
| B | HOH4964 |
| site_id | AC7 |
| Number of Residues | 13 |
| Details | BINDING SITE FOR RESIDUE PYR C 2603 |
| Chain | Residue |
| C | TYR2112 |
| C | ARG2165 |
| C | LEU2167 |
| C | LYS2183 |
| C | GLU2255 |
| C | ASP2256 |
| C | ASP2279 |
| C | ASN2421 |
| C | ASN2466 |
| C | ASN2467 |
| C | NAD2601 |
| C | MN2604 |
| C | HOH4904 |
| site_id | AC8 |
| Number of Residues | 14 |
| Details | BINDING SITE FOR RESIDUE PYR D 3603 |
| Chain | Residue |
| D | TYR3112 |
| D | ARG3165 |
| D | LEU3167 |
| D | LYS3183 |
| D | GLU3255 |
| D | ASP3256 |
| D | ASP3279 |
| D | ASN3421 |
| D | ASN3466 |
| D | ASN3467 |
| D | NAD3601 |
| D | MN3604 |
| D | HOH4001 |
| D | HOH5039 |
| site_id | AC9 |
| Number of Residues | 34 |
| Details | BINDING SITE FOR RESIDUE NAD A 601 |
| Chain | Residue |
| A | GLY446 |
| A | GLY465 |
| A | ASN466 |
| A | ASN467 |
| A | PYR603 |
| A | HOH4045 |
| A | HOH4124 |
| A | HOH4126 |
| A | HOH4186 |
| A | HOH4647 |
| A | HOH4891 |
| A | HOH5144 |
| A | ARG165 |
| A | LEU167 |
| A | GLY168 |
| A | ASN259 |
| A | ASP279 |
| A | THR283 |
| A | LEU310 |
| A | GLY311 |
| A | ALA312 |
| A | GLY313 |
| A | GLU314 |
| A | ALA315 |
| A | ASP345 |
| A | LYS346 |
| A | VAL392 |
| A | ALA393 |
| A | GLY394 |
| A | ALA395 |
| A | LEU398 |
| A | LEU419 |
| A | SER420 |
| A | ASN421 |
| site_id | BC1 |
| Number of Residues | 14 |
| Details | BINDING SITE FOR RESIDUE NAD A 602 |
| Chain | Residue |
| A | GLY192 |
| A | ILE193 |
| A | ARG194 |
| A | ARG197 |
| A | ILE479 |
| A | LEU480 |
| A | ASN482 |
| A | ARG542 |
| A | TYR552 |
| A | ARG556 |
| A | HOH4030 |
| D | ASP3244 |
| D | ARG3245 |
| D | GLY3247 |
| site_id | BC2 |
| Number of Residues | 31 |
| Details | BINDING SITE FOR RESIDUE NAD B 1601 |
| Chain | Residue |
| B | ARG1165 |
| B | LEU1167 |
| B | GLY1168 |
| B | ASN1259 |
| B | ASP1279 |
| B | THR1283 |
| B | GLY1311 |
| B | ALA1312 |
| B | GLY1313 |
| B | GLU1314 |
| B | ALA1315 |
| B | ASP1345 |
| B | LYS1346 |
| B | VAL1392 |
| B | ALA1393 |
| B | GLY1394 |
| B | ALA1395 |
| B | LEU1398 |
| B | LEU1419 |
| B | SER1420 |
| B | ASN1421 |
| B | GLY1446 |
| B | GLY1465 |
| B | ASN1466 |
| B | ASN1467 |
| B | PYR1603 |
| B | HOH4075 |
| B | HOH4193 |
| B | HOH4412 |
| B | HOH4611 |
| B | HOH4972 |
| site_id | BC3 |
| Number of Residues | 14 |
| Details | BINDING SITE FOR RESIDUE NAD B 1602 |
| Chain | Residue |
| B | HIS1154 |
| B | LYS1156 |
| B | GLY1192 |
| B | ILE1193 |
| B | ARG1194 |
| B | ARG1197 |
| B | ILE1479 |
| B | LEU1480 |
| B | ARG1542 |
| B | TYR1552 |
| B | ARG1556 |
| C | ASP2244 |
| C | GLY2247 |
| C | HOH4569 |
| site_id | BC4 |
| Number of Residues | 31 |
| Details | BINDING SITE FOR RESIDUE NAD C 2601 |
| Chain | Residue |
| C | ARG2165 |
| C | LEU2167 |
| C | GLY2168 |
| C | ASN2259 |
| C | ASP2279 |
| C | THR2283 |
| C | LEU2310 |
| C | ALA2312 |
| C | GLY2313 |
| C | GLU2314 |
| C | ALA2315 |
| C | ASP2345 |
| C | LYS2346 |
| C | VAL2392 |
| C | ALA2393 |
| C | GLY2394 |
| C | ALA2395 |
| C | LEU2419 |
| C | SER2420 |
| C | ASN2421 |
| C | GLY2446 |
| C | GLY2465 |
| C | ASN2466 |
| C | ASN2467 |
| C | PYR2603 |
| C | HOH4015 |
| C | HOH4125 |
| C | HOH4312 |
| C | HOH4385 |
| C | HOH4469 |
| C | HOH4685 |
| site_id | BC5 |
| Number of Residues | 16 |
| Details | BINDING SITE FOR RESIDUE NAD C 2602 |
| Chain | Residue |
| B | ASP1244 |
| B | ARG1245 |
| B | GLY1247 |
| C | HIS2154 |
| C | LYS2156 |
| C | GLY2192 |
| C | ILE2193 |
| C | ARG2194 |
| C | ARG2197 |
| C | ILE2479 |
| C | LEU2480 |
| C | ASN2482 |
| C | ARG2542 |
| C | TYR2552 |
| C | ARG2556 |
| C | HOH4556 |
| site_id | BC6 |
| Number of Residues | 30 |
| Details | BINDING SITE FOR RESIDUE NAD D 3601 |
| Chain | Residue |
| D | ARG3165 |
| D | LEU3167 |
| D | GLY3168 |
| D | ASN3259 |
| D | ASP3279 |
| D | THR3283 |
| D | GLY3311 |
| D | ALA3312 |
| D | GLY3313 |
| D | GLU3314 |
| D | ALA3315 |
| D | ASP3345 |
| D | LYS3346 |
| D | VAL3392 |
| D | ALA3393 |
| D | GLY3394 |
| D | ALA3395 |
| D | LEU3398 |
| D | LEU3419 |
| D | ASN3421 |
| D | GLY3446 |
| D | GLY3465 |
| D | ASN3466 |
| D | ASN3467 |
| D | PYR3603 |
| D | HOH4082 |
| D | HOH4470 |
| D | HOH4477 |
| D | HOH4498 |
| D | HOH5038 |
| site_id | BC7 |
| Number of Residues | 14 |
| Details | BINDING SITE FOR RESIDUE NAD D 3602 |
| Chain | Residue |
| A | ASP244 |
| A | ARG245 |
| A | GLY247 |
| D | HIS3154 |
| D | GLY3192 |
| D | ILE3193 |
| D | ARG3194 |
| D | ARG3197 |
| D | ILE3479 |
| D | LEU3480 |
| D | ASN3482 |
| D | ARG3542 |
| D | TYR3552 |
| D | ARG3556 |
| site_id | BC8 |
| Number of Residues | 9 |
| Details | BINDING SITE FOR RESIDUE FUM A 700 |
| Chain | Residue |
| A | GLN64 |
| A | ARG67 |
| A | ARG91 |
| A | HOH4071 |
| A | HOH4374 |
| A | HOH4394 |
| B | PHE1127 |
| B | ARG1128 |
| B | HOH4198 |
| site_id | BC9 |
| Number of Residues | 11 |
| Details | BINDING SITE FOR RESIDUE FUM B 1700 |
| Chain | Residue |
| A | PHE127 |
| B | GLN1064 |
| B | ARG1067 |
| B | ILE1088 |
| B | ARG1091 |
| B | LEU1095 |
| B | HOH4031 |
| B | HOH4038 |
| B | HOH4094 |
| B | HOH4139 |
| B | HOH4332 |
| site_id | CC1 |
| Number of Residues | 10 |
| Details | BINDING SITE FOR RESIDUE FUM C 2700 |
| Chain | Residue |
| C | GLN2064 |
| C | ARG2067 |
| C | ARG2091 |
| C | LEU2095 |
| C | HOH4005 |
| C | HOH4014 |
| C | HOH4034 |
| C | HOH4036 |
| C | HOH4254 |
| D | PHE3127 |
| site_id | CC2 |
| Number of Residues | 9 |
| Details | BINDING SITE FOR RESIDUE FUM D 3700 |
| Chain | Residue |
| C | PHE2127 |
| D | GLN3064 |
| D | ARG3067 |
| D | ARG3091 |
| D | HOH4035 |
| D | HOH4059 |
| D | HOH4081 |
| D | HOH4098 |
| D | HOH4119 |
Functional Information from PROSITE/UniProt
| site_id | PS00331 |
| Number of Residues | 17 |
| Details | MALIC_ENZYMES Malic enzymes signature. FnDDiqGTAaVaLAGLL |
| Chain | Residue | Details |
| A | PHE276-LEU292 |
Functional Information from SwissProt/UniProt
| site_id | SWS_FT_FI1 |
| Number of Residues | 4 |
| Details | ACT_SITE: Proton donor => ECO:0000269|PubMed:12962632 |
| Chain | Residue | Details |
| A | TYR112 | |
| B | TYR1112 | |
| C | TYR2112 | |
| D | TYR3112 |
| site_id | SWS_FT_FI2 |
| Number of Residues | 4 |
| Details | ACT_SITE: Proton acceptor => ECO:0000269|PubMed:12962632 |
| Chain | Residue | Details |
| A | LYS183 | |
| B | LYS1183 | |
| C | LYS2183 | |
| D | LYS3183 |
| site_id | SWS_FT_FI3 |
| Number of Residues | 8 |
| Details | BINDING: BINDING => ECO:0000269|PubMed:12121650, ECO:0000269|PubMed:12962632 |
| Chain | Residue | Details |
| A | ARG67 | |
| A | ARG91 | |
| B | ARG1067 | |
| B | ARG1091 | |
| C | ARG2067 | |
| C | ARG2091 | |
| D | ARG3067 | |
| D | ARG3091 |
| site_id | SWS_FT_FI4 |
| Number of Residues | 12 |
| Details | BINDING: BINDING => ECO:0000269|PubMed:12962632 |
| Chain | Residue | Details |
| A | ARG165 | |
| D | ARG3165 | |
| D | ASN3421 | |
| D | ASN3466 | |
| A | ASN421 | |
| A | ASN466 | |
| B | ARG1165 | |
| B | ASN1421 | |
| B | ASN1466 | |
| C | ARG2165 | |
| C | ASN2421 | |
| C | ASN2466 |
| site_id | SWS_FT_FI5 |
| Number of Residues | 12 |
| Details | BINDING: BINDING => ECO:0000269|PubMed:10700286, ECO:0000269|PubMed:12121650, ECO:0000269|PubMed:12962632 |
| Chain | Residue | Details |
| A | GLU255 | |
| D | GLU3255 | |
| D | ASP3256 | |
| D | ASP3279 | |
| A | ASP256 | |
| A | ASP279 | |
| B | GLU1255 | |
| B | ASP1256 | |
| B | ASP1279 | |
| C | GLU2255 | |
| C | ASP2256 | |
| C | ASP2279 |
| site_id | SWS_FT_FI6 |
| Number of Residues | 8 |
| Details | BINDING: BINDING => ECO:0000269|PubMed:10700286, ECO:0000269|PubMed:12962632 |
| Chain | Residue | Details |
| A | ASN259 | |
| A | GLY311 | |
| B | ASN1259 | |
| B | GLY1311 | |
| C | ASN2259 | |
| C | GLY2311 | |
| D | ASN3259 | |
| D | GLY3311 |
| site_id | SWS_FT_FI7 |
| Number of Residues | 20 |
| Details | MOD_RES: N6-acetyllysine => ECO:0007744|PubMed:19608861 |
| Chain | Residue | Details |
| A | LYS156 | |
| B | LYS1346 | |
| C | LYS2156 | |
| C | LYS2224 | |
| C | LYS2240 | |
| C | LYS2272 | |
| C | LYS2346 | |
| D | LYS3156 | |
| D | LYS3224 | |
| D | LYS3240 | |
| D | LYS3272 | |
| A | LYS224 | |
| D | LYS3346 | |
| A | LYS240 | |
| A | LYS272 | |
| A | LYS346 | |
| B | LYS1156 | |
| B | LYS1224 | |
| B | LYS1240 | |
| B | LYS1272 |
Catalytic Information from CSA
| site_id | CSA1 |
| Number of Residues | 3 |
| Details | Annotated By Reference To The Literature 1do8 |
| Chain | Residue | Details |
| A | ASP278 | |
| A | LYS183 | |
| A | TYR112 |
| site_id | CSA2 |
| Number of Residues | 3 |
| Details | Annotated By Reference To The Literature 1do8 |
| Chain | Residue | Details |
| B | LYS1183 | |
| B | ASP1278 | |
| B | TYR1112 |
| site_id | CSA3 |
| Number of Residues | 3 |
| Details | Annotated By Reference To The Literature 1do8 |
| Chain | Residue | Details |
| C | ASP2278 | |
| C | LYS2183 | |
| C | TYR2112 |
| site_id | CSA4 |
| Number of Residues | 3 |
| Details | Annotated By Reference To The Literature 1do8 |
| Chain | Residue | Details |
| D | ASP3278 | |
| D | TYR3112 | |
| D | LYS3183 |
| site_id | MCSA1 |
| Number of Residues | 8 |
| Details | M-CSA 21 |
| Chain | Residue | Details |
| A | TYR112 | electrostatic stabiliser, hydrogen bond acceptor, hydrogen bond donor, proton acceptor, proton donor |
| A | ARG165 | electrostatic stabiliser, hydrogen bond donor |
| A | LYS183 | electrostatic stabiliser, hydrogen bond donor, proton acceptor, proton donor, proton relay |
| A | GLU255 | metal ligand |
| A | ASP256 | metal ligand |
| A | ASP278 | hydrogen bond acceptor, proton acceptor, proton donor |
| A | ASP279 | metal ligand |
| A | ASN421 | electrostatic stabiliser, hydrogen bond donor |
| site_id | MCSA2 |
| Number of Residues | 8 |
| Details | M-CSA 21 |
| Chain | Residue | Details |
| B | TYR1112 | electrostatic stabiliser, hydrogen bond acceptor, hydrogen bond donor, proton acceptor, proton donor |
| B | ARG1165 | electrostatic stabiliser, hydrogen bond donor |
| B | LYS1183 | electrostatic stabiliser, hydrogen bond donor, proton acceptor, proton donor, proton relay |
| B | GLU1255 | metal ligand |
| B | ASP1256 | metal ligand |
| B | ASP1278 | hydrogen bond acceptor, proton acceptor, proton donor |
| B | ASP1279 | metal ligand |
| B | ASN1421 | electrostatic stabiliser, hydrogen bond donor |
| site_id | MCSA3 |
| Number of Residues | 8 |
| Details | M-CSA 21 |
| Chain | Residue | Details |
| C | TYR2112 | electrostatic stabiliser, hydrogen bond acceptor, hydrogen bond donor, proton acceptor, proton donor |
| C | ARG2165 | electrostatic stabiliser, hydrogen bond donor |
| C | LYS2183 | electrostatic stabiliser, hydrogen bond donor, proton acceptor, proton donor, proton relay |
| C | GLU2255 | metal ligand |
| C | ASP2256 | metal ligand |
| C | ASP2278 | hydrogen bond acceptor, proton acceptor, proton donor |
| C | ASP2279 | metal ligand |
| C | ASN2421 | electrostatic stabiliser, hydrogen bond donor |
| site_id | MCSA4 |
| Number of Residues | 8 |
| Details | M-CSA 21 |
| Chain | Residue | Details |
| D | TYR3112 | electrostatic stabiliser, hydrogen bond acceptor, hydrogen bond donor, proton acceptor, proton donor |
| D | ARG3165 | electrostatic stabiliser, hydrogen bond donor |
| D | LYS3183 | electrostatic stabiliser, hydrogen bond donor, proton acceptor, proton donor, proton relay |
| D | GLU3255 | metal ligand |
| D | ASP3256 | metal ligand |
| D | ASP3278 | hydrogen bond acceptor, proton acceptor, proton donor |
| D | ASP3279 | metal ligand |
| D | ASN3421 | electrostatic stabiliser, hydrogen bond donor |
