Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T76213 | Target Info | |||
| Target Name | Phenylalanine hydroxylase (PAH) | ||||
| Synonyms | Phenylalanine4hydroxylase; Phenylalanine-4-hydroxylase; Phe4monooxygenase; Phe-4-monooxygenase | ||||
| Target Type | Successful Target | ||||
| Gene Name | PAH | ||||
| Biochemical Class | Paired donor oxygen oxidoreductase | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: Norepinephrine | Ligand Info | |||||
| Structure Description | HUMAN PHENYLALANINE HYDROXYLASE CATALYTIC DOMAIN DIMER WITH BOUND NOR-ADRENALINE INHIBITOR | PDB:4PAH | ||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | No | [1] |
| PDB Sequence |
TVPWFPRTIQ
126 ELDRFANQIL136 SYGAELDADH146 PGFKDPVYRA156 RRKQFADIAY166 NYRHGQPIPR 176 VEYMEEEKKT186 WGTVFKTLKS196 LYKTHACYEY206 NHIFPLLEKY216 CGFHEDNIPQ 226 LEDVSQFLQT236 CTGFRLRPVA246 GLLSSRDFLG256 GLAFRVFHCT266 QYIRHGSKPM 276 YTPEPDICHE286 LLGHVPLFSD296 RSFAQFSQEI306 GLASLGAPDE316 YIEKLATIYW 326 FTVEFGLCKQ336 GDSIKAYGAG346 LLSSFGELQY356 CLSEKPKLLP366 LELEKTAIQN 376 YTVTEFQPLY386 YVAESFNDAK396 EKVRNFAATI406 PRPFSVRYDP416 YTQRIEVL |
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| Ligand Name: Dopamine | Ligand Info | |||||
| Structure Description | HUMAN PHENYLALANINE HYDROXYLASE CATALYTIC DOMAIN DIMER WITH BOUND DOPAMINE INHIBITOR | PDB:5PAH | ||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | No | [1] |
| PDB Sequence |
TVPWFPRTIQ
126 ELDRFANQIL136 SYGAELDADH146 PGFKDPVYRA156 RRKQFADIAY166 NYRHGQPIPR 176 VEYMEEEKKT186 WGTVFKTLKS196 LYKTHACYEY206 NHIFPLLEKY216 CGFHEDNIPQ 226 LEDVSQFLQT236 CTGFRLRPVA246 GLLSSRDFLG256 GLAFRVFHCT266 QYIRHGSKPM 276 YTPEPDICHE286 LLGHVPLFSD296 RSFAQFSQEI306 GLASLGAPDE316 YIEKLATIYW 326 FTVEFGLCKQ336 GDSIKAYGAG346 LLSSFGELQY356 CLSEKPKLLP366 LELEKTAIQN 376 YTVTEFQPLY386 YVAESFNDAK396 EKVRNFAATI406 PRPFSVRYDP416 YTQRIEVL |
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| Ligand Name: Levodopa | Ligand Info | |||||
| Structure Description | HUMAN PHENYLALANINE HYDROXYLASE CATALYTIC DOMAIN DIMER WITH BOUND L-DOPA (3,4-DIHYDROXYPHENYLALANINE) INHIBITOR | PDB:6PAH | ||||
| Method | X-ray diffraction | Resolution | 2.15 Å | Mutation | No | [1] |
| PDB Sequence |
TVPWFPRTIQ
126 ELDRFANQIL136 SYGAELDADH146 PGFKDPVYRA156 RRKQFADIAY166 NYRHGQPIPR 176 VEYMEEEKKT186 WGTVFKTLKS196 LYKTHACYEY206 NHIFPLLEKY216 CGFHEDNIPQ 226 LEDVSQFLQT236 CTGFRLRPVA246 GLLSSRDFLG256 GLAFRVFHCT266 QYIRHGSKPM 276 YTPEPDICHE286 LLGHVPLFSD296 RSFAQFSQEI306 GLASLGAPDE316 YIEKLATIYW 326 FTVEFGLCKQ336 GDSIKAYGAG346 LLSSFGELQY356 CLSEKPKLLP366 LELEKTAIQN 376 YTVTEFQPLY386 YVAESFNDAK396 EKVRNFAATI406 PRPFSVRYDP416 YTQRIEVL |
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .DAH or .DAH2 or .DAH3 or :3DAH;style chemicals stick;color identity;select .A:248 or .A:249 or .A:251 or .A:254 or .A:263 or .A:281 or .A:285 or .A:290 or .A:325 or .A:330; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: L-phenylalanine | Ligand Info | |||||
| Structure Description | Structure of a human aspartate kinase, chorismate mutase and TyrA domain. | PDB:5FII | ||||
| Method | X-ray diffraction | Resolution | 1.80 Å | Mutation | No | [2] |
| PDB Sequence |
AISLIFSLKE
43 EVGALAKVLR53 LFEENDVNLT63 HIESRPSRLK73 KDEYEFFTHL83 DKRSLPALTN 93 IIKILRHDIG103 ATVHEL
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .PHE or .PHE2 or .PHE3 or :3PHE;style chemicals stick;color identity;select .A:60 or .A:61 or .A:62 or .A:63 or .A:64 or .A:65; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: Norleucine | Ligand Info | |||||
| Structure Description | Crystal structure of ternary complex of the catalytic domain of human phenylalanine hydroxylase (Fe(II)) complexed with tetrahydrobiopterin and norleucine | PDB:1MMT | ||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | No | [3] |
| PDB Sequence |
TVPWFPRTIQ
126 ELDRFANQIL136 SYGAELDADH146 PGFKDPVYRA156 RRKQFADIAY166 NYRHGQPIPR 176 VEYMEEEKKT186 WGTVFKTLKS196 LYKTHACYEY206 NHIFPLLEKY216 CGFHEDNIPQ 226 LEDVSQFLQT236 CTGFRLRPVA246 GLLSSRDFLG256 GLAFRVFHCT266 QYIRHGSKPM 276 YTPEPDICHE286 LLGHVPLFSD296 RSFAQFSQEI306 GLASLGAPDE316 YIEKLATIYW 326 FTVEFGLCKQ336 GDSIKAYGAG346 LLSSFGELQY356 CLSEKPKLLP366 LELEKTAIQN 376 YTVTEFQPLY386 YVAESFNDAK396 EKVRNFAATI406 PRPFSVRYDP416 YTQRIEVL |
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .NLE or .NLE2 or .NLE3 or :3NLE;style chemicals stick;color identity;select .A:138 or .A:270 or .A:276 or .A:277 or .A:278 or .A:279 or .A:280 or .A:281 or .A:282 or .A:285 or .A:326 or .A:330 or .A:331 or .A:346 or .A:349 or .A:350 or .A:353; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: BH4 | Ligand Info | |||||
| Structure Description | Catalytic Domain of Human Phenylalanine Hydroxylase Fe(II) in Complex with Tetrahydrobiopterin | PDB:1J8U | ||||
| Method | X-ray diffraction | Resolution | 1.50 Å | Mutation | No | [4] |
| PDB Sequence |
VPWFPRTIQE
127 LDRFANQILS137 YGAELDADHP147 GFKDPVYRAR157 RKQFADIAYN167 YRHGQPIPRV 177 EYMEEEKKTW187 GTVFKTLKSL197 YKTHACYEYN207 HIFPLLEKYC217 GFHEDNIPQL 227 EDVSQFLQTC237 TGFRLRPVAG247 LLSSRDFLGG257 LAFRVFHCTQ267 YIRHGSKPMY 277 TPEPDICHEL287 LGHVPLFSDR297 SFAQFSQEIG307 LASLGAPDEY317 IEKLATIYWF 327 TVEFGLCKQG337 DSIKAYGAGL347 LSSFGELQYC357 LSEKPKLLPL367 ELEKTAIQNY 377 TVTEFQPLYY387 VAESFNDAKE397 KVRNFAATIP407 RPFSVRYDPY417 TQRIEVL |
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .H4B or .H4B2 or .H4B3 or :3H4B;style chemicals stick;color identity;select .A:245 or .A:247 or .A:248 or .A:249 or .A:250 or .A:251 or .A:254 or .A:255 or .A:263 or .A:264 or .A:281 or .A:286 or .A:290 or .A:322 or .A:325 or .A:330; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: 7,8-dihydrobiopterin | Ligand Info | |||||
| Structure Description | CRYSTAL STRUCTURE OF DOUBLE TRUNCATED HUMAN PHENYLALANINE HYDROXYLASE WITH BOUND 7,8-DIHYDRO-L-BIOPTERIN | PDB:1DMW | ||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | No | [5] |
| PDB Sequence |
VPWFPRTIQE
127 LDRFANQILS137 YGAELDADHP147 GFKDPVYRAR157 RKQFADIAYN167 YRHGQPIPRV 177 EYMEEEKKTW187 GTVFKTLKSL197 YKTHACYEYN207 HIFPLLEKYC217 GFHEDNIPQL 227 EDVSQFLQTC237 TGFRLRPVAG247 LLSSRDFLGG257 LAFRVFHCTQ267 YIRHGSKPMY 277 TPEPDICHEL287 LGHVPLFSDR297 SFAQFSQEIG307 LASLGAPDEY317 IEKLATIYWF 327 TVEFGLCKQG337 DSIKAYGAGL347 LSSFGELQYC357 LSEKPKLLPL367 ELEKTAIQNY 377 TVTEFQPLYY387 VAESFNDAKE397 KVRNFAATIP407 RPFSVRYDPY417 TQRIEVL |
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .HBI or .HBI2 or .HBI3 or :3HBI;style chemicals stick;color identity;select .A:245 or .A:247 or .A:248 or .A:249 or .A:250 or .A:251 or .A:254 or .A:255 or .A:263 or .A:264 or .A:281 or .A:290 or .A:322 or .A:323 or .A:325 or .A:326 or .A:330 or .A:377; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: 3-(2-Thienyl)-L-alanine | Ligand Info | |||||
| Structure Description | Crystal structure of ternary complex of the catalytic domain of human phenylalanine hydroxylase ((FeII)) complexed with tetrahydrobiopterin and thienylalanine | PDB:1MMK | ||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | No | [3] |
| PDB Sequence |
TVPWFPRTIQ
126 ELDRFANQIL136 SYGAELDADH146 PGFKDPVYRA156 RRKQFADIAY166 NYRHGQPIPR 176 VEYMEEEKKT186 WGTVFKTLKS196 LYKTHACYEY206 NHIFPLLEKY216 CGFHEDNIPQ 226 LEDVSQFLQT236 CTGFRLRPVA246 GLLSSRDFLG256 GLAFRVFHCT266 QYIRHGSKPM 276 YTPEPDICHE286 LLGHVPLFSD296 RSFAQFSQEI306 GLASLGAPDE316 YIEKLATIYW 326 FTVEFGLCKQ336 GDSIKAYGAG346 LLSSFGELQY356 CLSEKPKLLP366 LELEKTAIQN 376 YTVTEFQPLY386 YVAESFNDAK396 EKVRNFAATI406 PRPFSVRYDP416 YTQRIEVLD |
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .TIH or .TIH2 or .TIH3 or :3TIH;style chemicals stick;color identity;select .A:138 or .A:270 or .A:276 or .A:277 or .A:278 or .A:279 or .A:280 or .A:281 or .A:282 or .A:285 or .A:326 or .A:330 or .A:331 or .A:346 or .A:349 or .A:350 or .A:353; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: 5,6-Dimethyl-3-(4-methyl-2-pyridinyl)-2-thioxo-2,3-dihydrothieno[2,3-D]pyrimidin-4(1H)-one | Ligand Info | |||||
| Structure Description | Crystal structure of human phenylalanine hydroxylase in complex with a pharmacological chaperone | PDB:4ANP | ||||
| Method | X-ray diffraction | Resolution | 2.11 Å | Mutation | No | [6] |
| PDB Sequence |
TVPWFPRTIQ
126 ELDRFANQIL136 SYGAELDADH146 PGFKDPVYRA156 RRKQFADIAY166 NYRHGQPIPR 176 VEYMEEEKKT186 WGTVFKTLKS196 LYKTHACYEY206 NHIFPLLEKY216 CGFHEDNIPQ 226 LEDVSQFLQT236 CTGFRLRPVA246 GLLSSRDFLG256 GLAFRVFHCT266 QYIRHGSKPM 276 YTPEPDICHE286 LLGHVPLFSD296 RSFAQFSQEI306 GLASLGAPDE316 YIEKLATIYW 326 FTVEFGLCKQ336 GDSIKAYGAG346 LLSSFGELQY356 CLSEKPKLLP366 LELEKTAIQN 376 YTVTEFQPLY386 YVAESFNDAK396 EKVRNFAATI406 PRPFSVRYDP416 YTQRIEVLD |
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .3QI or .3QI2 or .3QI3 or :33QI;style chemicals stick;color identity;select .A:248 or .A:249 or .A:250 or .A:251 or .A:254 or .A:255 or .A:263 or .A:278 or .A:279 or .A:280 or .A:281 or .A:285 or .A:290 or .A:322 or .A:325 or .A:326 or .A:330; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: (S)-adrenaline | Ligand Info | |||||
| Structure Description | HUMAN PHENYLALANINE HYDROXYLASE CATALYTIC DOMAIN DIMER WITH BOUND ADRENALINE INHIBITOR | PDB:3PAH | ||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | No | [1] |
| PDB Sequence |
TVPWFPRTIQ
126 ELDRFANQIL136 SYGAELDADH146 PGFKDPVYRA156 RRKQFADIAY166 NYRHGQPIPR 176 VEYMEEEKKT186 WGTVFKTLKS196 LYKTHACYEY206 NHIFPLLEKY216 CGFHEDNIPQ 226 LEDVSQFLQT236 CTGFRLRPVA246 GLLSSRDFLG256 GLAFRVFHCT266 QYIRHGSKPM 276 YTPEPDICHE286 LLGHVPLFSD296 RSFAQFSQEI306 GLASLGAPDE316 YIEKLATIYW 326 FTVEFGLCKQ336 GDSIKAYGAG346 LLSSFGELQY356 CLSEKPKLLP366 LELEKTAIQN 376 YTVTEFQPLY386 YVAESFNDAK396 EKVRNFAATI406 PRPFSVRYDP416 YTQRIEVL |
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .XDE or .XDE2 or .XDE3 or :3XDE;style chemicals stick;color identity;select .A:248 or .A:249 or .A:250 or .A:251 or .A:254 or .A:263 or .A:281 or .A:285 or .A:290 or .A:325 or .A:330; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 4a-Carbinolamine tetrahydrobiopterin | Ligand Info | |||||
| Structure Description | Crystal structure of phenylalanine hydroxylase A313T mutant with 7,8-dihydrobiopterin bound | PDB:1TG2 | ||||
| Method | X-ray diffraction | Resolution | 2.20 Å | Mutation | Yes | [7] |
| PDB Sequence |
TVPWFPRTIQ
126 ELDRFANQIL136 SYGAELDADH146 PGFKDPVYRA156 RRKQFADIAY166 NYRHGQPIPR 176 VEYMEEEKKT186 WGTVFKTLKS196 LYKTHACYEY206 NHIFPLLEKY216 CGFHEDNIPQ 226 LEDVSQFLQT236 CTGFRLRPVA246 GLLSSRDFLG256 GLAFRVFHCT266 QYIRHGSKPM 276 YTPEPDICHE286 LLGHVPLFSD296 RSFAQFSQEI306 GLASLGTPDE316 YIEKLATIYW 326 FTVEFGLCKQ336 GDSIKAYGAG346 LLSSFGELQY356 CLSEKPKLLP366 LELEKTAIQN 376 YTVTEFQPLY386 YVAESFNDAK396 EKVRNFAATI406 PRPFSVRYDP416 YTQRIEVL |
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .H2B or .H2B2 or .H2B3 or :3H2B;style chemicals stick;color identity;select .A:245 or .A:247 or .A:248 or .A:249 or .A:250 or .A:251 or .A:254 or .A:255 or .A:264 or .A:266 or .A:281 or .A:286 or .A:290 or .A:322 or .A:325 or .A:330; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Crystallographic analysis of the human phenylalanine hydroxylase catalytic domain with bound catechol inhibitors at 2.0 A resolution. Biochemistry. 1998 Nov 10;37(45):15638-46. | ||||
| REF 2 | Structural basis for ligand-dependent dimerization of phenylalanine hydroxylase regulatory domain. Sci Rep. 2016 Apr 6;6:23748. | ||||
| REF 3 | 2.0A resolution crystal structures of the ternary complexes of human phenylalanine hydroxylase catalytic domain with tetrahydrobiopterin and 3-(2-thienyl)-L-alanine or L-norleucine: substrate specificity and molecular motions related to substrate binding. J Mol Biol. 2003 Oct 31;333(4):747-57. | ||||
| REF 4 | High resolution crystal structures of the catalytic domain of human phenylalanine hydroxylase in its catalytically active Fe(II) form and binary complex with tetrahydrobiopterin. J Mol Biol. 2001 Nov 23;314(2):279-91. | ||||
| REF 5 | Crystal structure and site-specific mutagenesis of pterin-bound human phenylalanine hydroxylase. Biochemistry. 2000 Mar 7;39(9):2208-17. | ||||
| REF 6 | Structural and mechanistic basis of the interaction between a pharmacological chaperone and human phenylalanine hydroxylase. Chembiochem. 2012 Jun 18;13(9):1266-9. | ||||
| REF 7 | Correction of kinetic and stability defects by tetrahydrobiopterin in phenylketonuria patients with certain phenylalanine hydroxylase mutations. Proc Natl Acad Sci U S A. 2004 Nov 30;101(48):16903-8. | ||||
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