SitesBLAST
Comparing GFF4633 FitnessBrowser__WCS417:GFF4633 to proteins with known functional sites using BLASTp with E ≤ 0.001.
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Found 20 (the maximum) hits to proteins with known functional sites (download)
Q1LK00 Tryptophan 2,3-dioxygenase; TDO; Tryptamin 2,3-dioxygenase; Tryptophan oxygenase; TO; TRPO; Tryptophan pyrrolase; Tryptophanase; EC 1.13.11.11 from Cupriavidus metallidurans (strain ATCC 43123 / DSM 2839 / NBRC 102507 / CH34) (Ralstonia metallidurans) (see paper)
71% identity, 95% coverage: 16:285/285 of query aligns to 30:299/299 of Q1LK00
- F68 (= F54) mutation to A: Abolishes catalytic activity.
- Y130 (= Y116) mutation to F: 15-fold increase in catalytic activity.
- R134 (= R120) mutation to A: Abolishes catalytic activity.
- T271 (= T257) mutation to A: Abolishes catalytic activity.
2noxB Crystal structure of tryptophan 2,3-dioxygenase from ralstonia metallidurans (see paper)
70% identity, 95% coverage: 16:285/285 of query aligns to 1:266/266 of 2noxB
- binding protoporphyrin ix containing fe: F39 (= F54), H43 (= H58), T46 (≠ S61), W90 (= W105), L93 (= L108), S112 (= S127), G113 (= G128), F114 (= F129), Y119 (= Y134), R120 (= R135), H228 (= H243), V232 (= V247), E242 (= E261), Y246 (= Y265), L247 (= L266)
2nw9A Crystal structure of tryptophan 2,3-dioxygenase (tdo) from xanthomonas campestris in complex with ferrous heme and 6-fluoro-tryptophan. Northeast structural genomics target xcr13 (see paper)
48% identity, 91% coverage: 27:285/285 of query aligns to 3:263/265 of 2nw9A
- binding 6-fluoro-l-tryptophan: F32 (= F54), H36 (= H58), Y94 (= Y116), R98 (= R120), L101 (= L123), S104 (= S126), G234 (= G256), T235 (= T257)
- binding protoporphyrin ix containing fe: F32 (= F54), H36 (= H58), S39 (= S61), W83 (= W105), L86 (= L108), G106 (= G128), F107 (= F129), Y112 (= Y134), R113 (= R135), H221 (= H243), V225 (= V247), I229 (= I251), G234 (= G256), G236 (= G258), S238 (≠ T260)
Q8PDA8 Tryptophan 2,3-dioxygenase; TDO; Tryptamin 2,3-dioxygenase; Tryptophan oxygenase; TO; TRPO; Tryptophan pyrrolase; Tryptophanase; EC 1.13.11.11 from Xanthomonas campestris pv. campestris (strain ATCC 33913 / DSM 3586 / NCPPB 528 / LMG 568 / P 25) (see 2 papers)
48% identity, 91% coverage: 27:285/285 of query aligns to 22:282/298 of Q8PDA8
- FIIQH 51:55 (= FIIQH 54:58) binding
- H55 (= H58) mutation to A: Decrease in catalytic efficiency using L-tryptophan, 5-fluoro-D/L-tryptophan, 6-fluoro-D/L-tryptophan, 5-methyl-D/L-tryptophan and 6-methyl-D/L-tryptophan as substrate.; mutation to S: Decrease in catalytic efficiency using L-tryptophan, 5-fluoro-D/L-tryptophan, 6-fluoro-D/L-tryptophan, 5-methyl-D/L-tryptophan and 6-methyl-D/L-tryptophan as substrate.
- Y113 (= Y116) binding
- R117 (= R120) binding
- H240 (= H243) binding axial binding residue
- T254 (= T257) binding
7p46A Crystal structure of xanthomonas campestris tryptophan 2,3-dioxygenase (tdo) (see paper)
48% identity, 91% coverage: 27:285/285 of query aligns to 18:278/281 of 7p46A
- binding protoporphyrin ix containing fe: S51 (≠ H58), S54 (= S61), W98 (= W105), S120 (= S127), G121 (= G128), F122 (= F129), Y127 (= Y134), R128 (= R135), H236 (= H243), V240 (= V247), G249 (= G256), G251 (= G258), S253 (≠ T260)
- binding (2S)-2-amino-4-(2-aminophenyl)-4-oxobutanoic acid: F47 (= F54), S51 (≠ H58), Y109 (= Y116), R113 (= R120), S119 (= S126), G249 (= G256), T250 (= T257)
- binding tryptophan: K82 (= K89), A85 (= A92), Y216 (= Y223), S217 (≠ Q224), E220 (= E227), D224 (= D231)
1yw0A Crystal structure of the tryptophan 2,3-dioxygenase from xanthomonas campestris. Northeast structural genomics target xcr13.
44% identity, 91% coverage: 28:285/285 of query aligns to 1:241/243 of 1yw0A
5ti9C Crystal structure of human tdo in complex with trp and dioxygen, northeast structural genomics consortium target hr6161 (see paper)
30% identity, 85% coverage: 27:267/285 of query aligns to 1:287/326 of 5ti9C
- binding protoporphyrin ix containing fe: H37 (= H58), Y40 (≠ S61), L93 (= L108), S112 (= S127), G113 (= G128), F114 (= F129), F119 (≠ Y134), R120 (= R135), W259 (= W239), H263 (= H243), V267 (= V247), M270 (≠ I250), G276 (= G256), G278 (= G258), S280 (≠ T260), L286 (= L266)
- binding N'-Formylkynurenine: F33 (= F54), H37 (= H58), R105 (= R120), L108 (= L123), A111 (≠ S126), S112 (= S127), G113 (= G128), L271 (≠ I251), G276 (= G256), T277 (= T257)
- binding tryptophan: R64 (≠ P85), E66 (≠ A87), W159 (≠ A165), R162 (vs. gap), T163 (= T168), P164 (= P169), I230 (vs. gap), F239 (≠ Y219), P242 (≠ L222)
6pyzC Crystal structure of human tryptophan 2,3-dioxygenase in complex with pf-06840003 in active site (see paper)
30% identity, 85% coverage: 26:267/285 of query aligns to 1:294/333 of 6pyzC
- binding (3S)-3-(5-fluoro-1H-indol-3-yl)pyrrolidine-2,5-dione: Y4 (= Y29), Y7 (= Y32), F34 (= F54), H38 (= H58), A112 (≠ S126), S113 (= S127), T284 (= T257)
- binding protoporphyrin ix containing fe: H38 (= H58), Y41 (≠ S61), L94 (= L108), G114 (= G128), F115 (= F129), F120 (≠ Y134), R121 (= R135), H270 (= H243), M273 (≠ T246), V274 (= V247), M277 (≠ I250), G283 (= G256), G285 (= G258), S287 (≠ T260), Y292 (= Y265), L293 (= L266)
- binding alpha-methyl-L-tryptophan: R65 (≠ P85), E67 (≠ A87), W167 (≠ A165), R170 (vs. gap), T171 (= T168), P172 (= P169), F246 (≠ Y219)
P20351 Tryptophan 2,3-dioxygenase; TDO; Protein vermilion; Tryptamin 2,3-dioxygenase; Tryptophan oxygenase; TO; TRPO; Tryptophan pyrrolase; Tryptophanase; EC 1.13.11.11 from Drosophila melanogaster (Fruit fly) (see paper)
28% identity, 94% coverage: 4:270/285 of query aligns to 3:340/379 of P20351
- D123 (≠ E115) mutation to A: Strongly reduced enzyme activity.
- Y236 (vs. gap) mutation to F: Strongly reduced enzyme activity.
- R309 (= R240) mutation to A: Strongly reduced enzyme activity.
- H312 (= H243) binding axial binding residue
- Y335 (= Y265) mutation to F: Strongly reduced enzyme activity.
4hkaA Crystal structure of drosophila melanogaster tryptophan 2,3- dioxygenase in complex with heme (see paper)
29% identity, 85% coverage: 29:270/285 of query aligns to 4:317/345 of 4hkaA
- binding protoporphyrin ix containing fe: H38 (= H58), Y41 (≠ S61), F45 (≠ M65), L93 (= L108), F101 (≠ Y116), F114 (= F129), Q115 (= Q130), F119 (≠ Y134), Y136 (≠ P151), W285 (= W239), H289 (= H243), V293 (= V247), Y312 (= Y265), L313 (= L266)
Q09474 Tryptophan 2,3-dioxygenase; TDO; Tryptamin 2,3-dioxygenase; Tryptophan oxygenase; TO; TRPO; Tryptophan pyrrolase; Tryptophanase; EC 1.13.11.11 from Caenorhabditis elegans (see paper)
26% identity, 88% coverage: 17:267/285 of query aligns to 29:351/403 of Q09474
- PLD 133:135 (≠ PSE 113:115) PLD motif; required for enzymatic activity; mutation Missing: Abolishes catalytic activity. Animals have an extended lifespan, an extended reproductive lifespan, have fewer hatched progeny and display increased motility.
6a4iD Crystal structure of human tdo inhibitor complex
32% identity, 79% coverage: 27:252/285 of query aligns to 1:248/290 of 6a4iD
- binding 1-(6-chloro-1H-indazol-4-yl)cyclohexan-1-ol: Y3 (= Y29), Y6 (= Y32), F33 (= F54), H37 (= H58), A111 (≠ S126)
- binding protoporphyrin ix containing fe: F33 (= F54), H37 (= H58), Y40 (≠ S61), F101 (≠ Y116), S112 (= S127), G113 (= G128), F114 (= F129), F119 (≠ Y134), H239 (= H243), V243 (= V247), M246 (≠ I250)
- binding tryptophan: R64 (≠ P85), W153 (≠ A165), R156 (vs. gap), T157 (= T168), P158 (= P169), I206 (vs. gap), F215 (≠ Y219)
Sites not aligning to the query:
6a4iB Crystal structure of human tdo inhibitor complex
30% identity, 85% coverage: 27:267/285 of query aligns to 1:275/309 of 6a4iB
- binding 1-(6-chloro-1H-indazol-4-yl)cyclohexan-1-ol: Y3 (= Y29), Y6 (= Y32), F33 (= F54), H37 (= H58), L108 (= L123), A111 (≠ S126)
- binding protoporphyrin ix containing fe: F33 (= F54), H37 (= H58), Y40 (≠ S61), L93 (= L108), S112 (= S127), G113 (= G128), F114 (= F129), F119 (≠ Y134), R120 (= R135), W255 (= W239), H259 (= H243), V263 (= V247), L274 (= L266)
- binding tryptophan: R64 (≠ P85), E66 (≠ A87), W153 (≠ A165), R156 (vs. gap), T157 (= T168), P158 (= P169), P238 (≠ L222)
6a4iA Crystal structure of human tdo inhibitor complex
29% identity, 84% coverage: 29:267/285 of query aligns to 3:293/322 of 6a4iA
- binding 1-(6-chloro-1H-indazol-4-yl)cyclohexan-1-ol: Y3 (= Y29), Y6 (= Y32), F33 (= F54), H37 (= H58), A111 (≠ S126)
- binding protoporphyrin ix containing fe: F33 (= F54), H37 (= H58), Y40 (≠ S61), L93 (= L108), F101 (≠ Y116), S112 (= S127), G113 (= G128), F114 (= F129), F119 (≠ Y134), W270 (= W239), H274 (= H243), M277 (≠ T246), V278 (= V247), M281 (≠ I250), L292 (= L266)
- binding tryptophan: R64 (≠ P85), W158 (≠ A165), R161 (vs. gap), T162 (= T168), P163 (= P169), I241 (vs. gap), F250 (≠ Y219), P253 (≠ L222)
8qv7B Crystal structure of human tdo with alpha-methyl-l-tryptophan
30% identity, 79% coverage: 27:252/285 of query aligns to 1:272/310 of 8qv7B
Sites not aligning to the query:
7lu7CCC Tryptophan 2,3-dioxygenase
28% identity, 80% coverage: 26:252/285 of query aligns to 1:279/323 of 7lu7CCC
- binding (1~{R})-1-cyclohexyl-2-[(5~{S})-5~{H}-imidazo[1,5-b]isoindol-5-yl]ethanol: Y4 (= Y29), Y7 (= Y32), F34 (= F54), H38 (= H58), A112 (≠ S126), G114 (= G128)
- binding protoporphyrin ix containing fe: H38 (= H58), Y41 (≠ S61), S113 (= S127), G114 (= G128), F115 (= F129), F120 (≠ Y134), R121 (= R135), W266 (= W239), H270 (= H243), V274 (= V247)
- binding alpha-methyl-L-tryptophan: R65 (≠ P85), E67 (≠ A87), W163 (≠ A165), R166 (vs. gap), T167 (= T168), P168 (= P169), F246 (≠ Y219), P249 (≠ L222)
5ti9D Crystal structure of human tdo in complex with trp and dioxygen, northeast structural genomics consortium target hr6161 (see paper)
41% identity, 41% coverage: 26:142/285 of query aligns to 1:128/332 of 5ti9D
- binding protoporphyrin ix containing fe: F34 (= F54), H38 (= H58), Y41 (≠ S61), L94 (= L108), S113 (= S127), G114 (= G128), F115 (= F129), F120 (≠ Y134), R121 (= R135)
- binding N'-Formylkynurenine: F34 (= F54), H38 (= H58), R106 (= R120), L109 (= L123), A112 (≠ S126), S113 (= S127), G114 (= G128)
- binding tryptophan: R65 (≠ P85), E67 (≠ A87)
Sites not aligning to the query:
- binding protoporphyrin ix containing fe: 137, 286, 289, 290, 300, 301
- binding tryptophan: 170, 173, 174, 175, 253, 262, 265
8r5qC Structure of apo tdo with a bound inhibitor
28% identity, 79% coverage: 27:252/285 of query aligns to 1:282/317 of 8r5qC
- binding 3-chloranyl-~{N}-[(1~{S})-1-(6-chloranylpyridin-3-yl)-2-phenyl-ethyl]aniline: Y3 (= Y29), Y6 (= Y32), L7 (= L33), F33 (= F54), H37 (= H58), F101 (≠ Y116), P110 (≠ Q125), G113 (= G128), Q115 (= Q130), S116 (= S131), H273 (= H243), V277 (= V247), M280 (≠ I250)
- binding alpha-methyl-L-tryptophan: R64 (≠ P85), E66 (≠ A87), W153 (≠ A165), R156 (vs. gap), P158 (= P169), F249 (≠ Y219)
P48775 Tryptophan 2,3-dioxygenase; TDO; Tryptamin 2,3-dioxygenase; Tryptophan oxygenase; TO; TRPO; Tryptophan pyrrolase; Tryptophanase; EC 1.13.11.11 from Homo sapiens (Human) (see 3 papers)
42% identity, 40% coverage: 29:142/285 of query aligns to 42:166/406 of P48775
- Y42 (= Y29) mutation to A: Reduces enzyme activity by 99%.
- Y45 (= Y32) mutation to A: Reduces enzyme activity by 99%.
- F72 (= F54) mutation to A: Abolishes enzyme activity.
- FIITH 72:76 (≠ FIIQH 54:58) binding
- H76 (= H58) mutation to A: Abolishes enzyme activity.
- M108 (= M90) to I: in HYPTRP; reduced tryptophan 2,3-dioxygenase activity; does not affect homotetramerization; dbSNP:rs1553957997
- F140 (≠ Y116) mutation to A: Reduces enzyme activity by 99%.
- R144 (= R120) binding ; mutation to A: Reduces enzyme activity by 99%.
- S151 (= S127) mutation to A: Reduces enzyme activity by 90%.
Sites not aligning to the query:
- 175 Y→G: Reduces enzyme activity.
- 328 binding axial binding residue; H→A: Abolishes enzyme activity.
- 342 binding
5ti9A Crystal structure of human tdo in complex with trp and dioxygen, northeast structural genomics consortium target hr6161 (see paper)
41% identity, 41% coverage: 26:142/285 of query aligns to 1:128/350 of 5ti9A
- binding protoporphyrin ix containing fe: F34 (= F54), H38 (= H58), Y41 (≠ S61), F102 (≠ Y116), S113 (= S127), G114 (= G128), F115 (= F129), F120 (≠ Y134), R121 (= R135)
- binding tryptophan: F34 (= F54), H38 (= H58), R65 (≠ P85), E67 (≠ A87), F102 (≠ Y116), R106 (= R120), L109 (= L123), A112 (≠ S126), S113 (= S127)
Sites not aligning to the query:
- binding protoporphyrin ix containing fe: 286, 290, 293, 294, 303, 305, 307, 313
- binding tryptophan: 170, 173, 174, 175, 266, 269, 303, 304
Query Sequence
>GFF4633 FitnessBrowser__WCS417:GFF4633
MSQCPFSADYQPPEEWHNAELNFSESMSYGDYLDLGKVLSAQHPLSPDHNEMLFIIQHQT
SELWMKLMLHELKAAREHVRLGELPPAFKMLARVSRIFDQLVHAWAVLATMTPSEYKSIR
PFLGQSSGFQSFQYREIEFILGNKSAALLRPHAHRPELLNELKVAIATPSLYDEAINLMI
QAGLAIDPKRAERDPTAATVHDESVEAAWREVYRDPSRYWDLYQLAEKFIDLEDSFRQWR
FRHVTTVERIIGFQPGTGGTEGVGYLRKMLDTVLFPELWRVRSTL
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SitesBLAST's Database
SitesBLAST's database includes
(1) SwissProt
entries with experimentally-supported functional features;
and (2) protein structures with bound ligands, from the
BioLip database.
by Morgan Price,
Arkin group
Lawrence Berkeley National Laboratory