6FMD
Targeting myeloid differentiation using potent human dihydroorotate dehydrogenase (hDHODH) inhibitors based on 2-hydroxypyrazolo[1,5-a]pyridine scaffold
Functional Information from GO Data
Chain | GOid | namespace | contents |
A | 0004151 | molecular_function | dihydroorotase activity |
A | 0004152 | molecular_function | dihydroorotate dehydrogenase activity |
A | 0005515 | molecular_function | protein binding |
A | 0005654 | cellular_component | nucleoplasm |
A | 0005737 | cellular_component | cytoplasm |
A | 0005739 | cellular_component | mitochondrion |
A | 0005743 | cellular_component | mitochondrial inner membrane |
A | 0005829 | cellular_component | cytosol |
A | 0006207 | biological_process | 'de novo' pyrimidine nucleobase biosynthetic process |
A | 0006221 | biological_process | pyrimidine nucleotide biosynthetic process |
A | 0006225 | biological_process | UDP biosynthetic process |
A | 0009220 | biological_process | pyrimidine ribonucleotide biosynthetic process |
A | 0016020 | cellular_component | membrane |
A | 0016491 | molecular_function | oxidoreductase activity |
A | 0016627 | molecular_function | oxidoreductase activity, acting on the CH-CH group of donors |
A | 0044205 | biological_process | 'de novo' UMP biosynthetic process |
A | 0106430 | molecular_function | dihydroorotate dehydrogenase (quinone) activity |
Functional Information from PDB Data
site_id | AC1 |
Number of Residues | 17 |
Details | binding site for residue DUH A 401 |
Chain | Residue |
A | MET43 |
A | LEU68 |
A | VAL134 |
A | ARG136 |
A | TYR356 |
A | LEU359 |
A | THR360 |
A | PRO364 |
A | HOH597 |
A | LEU46 |
A | GLN47 |
A | PRO52 |
A | ALA55 |
A | HIS56 |
A | ALA59 |
A | PHE62 |
A | LEU67 |
site_id | AC2 |
Number of Residues | 4 |
Details | binding site for residue CL A 402 |
Chain | Residue |
A | GLN165 |
A | PRO204 |
A | ARG298 |
A | SER299 |
site_id | AC3 |
Number of Residues | 3 |
Details | binding site for residue CL A 403 |
Chain | Residue |
A | ARG245 |
A | THR301 |
A | GLY302 |
site_id | AC4 |
Number of Residues | 25 |
Details | binding site for residue FMN A 404 |
Chain | Residue |
A | ALA95 |
A | ALA96 |
A | GLY97 |
A | LYS100 |
A | GLY119 |
A | SER120 |
A | ASN145 |
A | ASN181 |
A | ASN212 |
A | LYS255 |
A | THR283 |
A | ASN284 |
A | THR285 |
A | SER305 |
A | GLY306 |
A | LEU309 |
A | VAL333 |
A | GLY334 |
A | GLY335 |
A | LEU355 |
A | TYR356 |
A | THR357 |
A | ORO411 |
A | HOH522 |
A | HOH533 |
site_id | AC5 |
Number of Residues | 5 |
Details | binding site for residue ACT A 405 |
Chain | Residue |
A | ALA169 |
A | THR172 |
A | LEU205 |
A | ASP207 |
A | HOH517 |
site_id | AC6 |
Number of Residues | 3 |
Details | binding site for residue ACT A 406 |
Chain | Residue |
A | ARG241 |
A | ASP242 |
A | LEU275 |
site_id | AC7 |
Number of Residues | 1 |
Details | binding site for residue ACT A 407 |
Chain | Residue |
A | ARG246 |
site_id | AC8 |
Number of Residues | 7 |
Details | binding site for residue ACT A 408 |
Chain | Residue |
A | LYS307 |
A | PRO308 |
A | ASP311 |
A | THR314 |
A | GLN315 |
A | ARG318 |
A | HOH507 |
site_id | AC9 |
Number of Residues | 1 |
Details | binding site for residue ACT A 409 |
Chain | Residue |
A | HIS41 |
site_id | AD1 |
Number of Residues | 4 |
Details | binding site for residue ACT A 410 |
Chain | Residue |
A | GLN239 |
A | ASP242 |
A | GLY243 |
A | HOH503 |
site_id | AD2 |
Number of Residues | 9 |
Details | binding site for residue ORO A 411 |
Chain | Residue |
A | LYS100 |
A | ASN145 |
A | TYR147 |
A | GLY148 |
A | PHE149 |
A | ASN212 |
A | ASN284 |
A | THR285 |
A | FMN404 |
site_id | AD3 |
Number of Residues | 4 |
Details | binding site for residue GOL A 412 |
Chain | Residue |
A | GLY276 |
A | ARG327 |
A | HOH526 |
A | HOH565 |
site_id | AD4 |
Number of Residues | 3 |
Details | binding site for residue GOL A 413 |
Chain | Residue |
A | TYR109 |
A | LYS110 |
A | HOH603 |
site_id | AD5 |
Number of Residues | 3 |
Details | binding site for residue GOL A 414 |
Chain | Residue |
A | GLU127 |
A | ASN129 |
A | ARG131 |
site_id | AD6 |
Number of Residues | 3 |
Details | binding site for residue GOL A 415 |
Chain | Residue |
A | LYS124 |
A | SER155 |
A | GLU197 |
site_id | AD7 |
Number of Residues | 6 |
Details | binding site for residue PGE A 416 |
Chain | Residue |
A | HIS101 |
A | GLN126 |
A | GLU127 |
A | ASN150 |
A | SER151 |
A | PGE417 |
site_id | AD8 |
Number of Residues | 3 |
Details | binding site for residue PGE A 417 |
Chain | Residue |
A | ARG160 |
A | PGE416 |
A | HIS152 |
site_id | AD9 |
Number of Residues | 4 |
Details | binding site for residue PGE A 418 |
Chain | Residue |
A | ASP51 |
A | SER54 |
A | ARG57 |
A | HOH505 |
site_id | AE1 |
Number of Residues | 3 |
Details | binding site for residue PGE A 419 |
Chain | Residue |
A | ARG82 |
A | GLY326 |
A | SER351 |
site_id | AE2 |
Number of Residues | 6 |
Details | binding site for residue PGE A 420 |
Chain | Residue |
A | ARG246 |
A | ARG249 |
A | ASP278 |
A | HOH521 |
A | HOH567 |
A | HOH574 |
site_id | AE3 |
Number of Residues | 4 |
Details | binding site for residue PGE A 421 |
Chain | Residue |
A | ARG245 |
A | VAL287 |
A | SER288 |
A | ARG289 |
Functional Information from PROSITE/UniProt
Functional Information from SwissProt/UniProt
site_id | SWS_FT_FI1 |
Number of Residues | 9 |
Details | TOPO_DOM: Mitochondrial matrix => ECO:0000250 |
Chain | Residue | Details |
A | MET2-ALA11 |
site_id | SWS_FT_FI2 |
Number of Residues | 19 |
Details | TRANSMEM: Helical => ECO:0000250 |
Chain | Residue | Details |
A | GLN12-ALA31 |
site_id | SWS_FT_FI3 |
Number of Residues | 364 |
Details | TOPO_DOM: Mitochondrial intermembrane => ECO:0000250 |
Chain | Residue | Details |
A | THR32-ARG396 |
site_id | SWS_FT_FI4 |
Number of Residues | 1 |
Details | ACT_SITE: Nucleophile |
Chain | Residue | Details |
A | SER215 |
site_id | SWS_FT_FI5 |
Number of Residues | 9 |
Details | BINDING: BINDING => ECO:0000269|PubMed:10673429, ECO:0000269|PubMed:16480261 |
Chain | Residue | Details |
A | ALA96 | |
A | SER120 | |
A | ASN181 | |
A | ASN212 | |
A | LYS255 | |
A | THR283 | |
A | GLY306 | |
A | GLY335 | |
A | TYR356 |
site_id | SWS_FT_FI6 |
Number of Residues | 3 |
Details | BINDING: |
Chain | Residue | Details |
A | LYS100 | |
A | ASN145 | |
A | ASN284 |
Catalytic Information from CSA
site_id | MCSA1 |
Number of Residues | 7 |
Details | M-CSA 109 |
Chain | Residue | Details |
A | ASN145 | electrostatic stabiliser |
A | PHE149 | activator, electrostatic stabiliser, enhance reactivity, polar/non-polar interaction |
A | SER215 | electrostatic stabiliser, hydrogen bond acceptor, hydrogen bond donor, polar/non-polar interaction, proton acceptor, proton donor, proton relay |
A | ASN217 | electrostatic stabiliser |
A | THR218 | activator, electrostatic stabiliser, enhance reactivity, hydrogen bond acceptor |
A | LYS255 | electrostatic stabiliser, hydrogen bond donor |
A | ASN284 | electrostatic stabiliser |