Target Information
| Target General Information | Top | |||||
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| Target ID |
T71690
(Former ID: TTDS00530)
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| Target Name |
Bacterial Pyruvate decarboxylase (Bact aceE)
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| Synonyms |
aceE; Pyruvate decarboxylase E1 component
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| Gene Name |
Bact aceE
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Vitamin deficiency [ICD-11: 5B55-5B5F] | |||||
| Function |
The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-coa and co(2). It contains multiple copies of three enzymatic components: pyruvate dehydrogenase (e1), dihydrolipoamide acetyltransferase (e2) and lipoamide dehydrogenase.
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| BioChemical Class |
Aldehyde/oxo donor oxidoreductase
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| UniProt ID | ||||||
| Sequence |
MSERFPNDVDPIETRDWLQAIESVIREEGVERAQYLIDQLLAEARKGGVNVAAGTGISNY
INTIPVEEQPEYPGNLELERRIRSAIRWNAIMTVLRASKKDLELGGHMASFQSSATIYDV CFNHFFRARNEQDGGDLVYFQGHISPGVYARAFLEGRLTQEQLDNFRQEVHGNGLSSYPH PKLMPEFWQFPTVSMGLGPIGAIYQAKFLKYLEHRGLKDTSKQTVYAFLGDGEMDEPESK GAITIATREKLDNLVFVINCNLQRLDGPVTGNGKIINELEGIFEGAGWNVIKVMWGSRWD ELLRKDTSGKLIQLMNETVDGDYQTFKSKDGAYVREHFFGKYPETAALVADWTDEQIWAL NRGGHDPKKIYAAFKKAQETKGKATVILAHTIKGYGMGDAAEGKNIAHQVKKMNMDGVRH IRDRFNVPVSDADIEKLPYITFPEGSEEHTYLHAQRQKLHGYLPSRQPNFTEKLELPSLQ DFGALLEEQSKEISTTIAFVRALNVMLKNKSIKDRLVPIIADEARTFGMEGLFRQIGIYS PNGQQYTPQDREQVAYYKEDEKGQILQEGINELGAGCSWLAAATSYSTNNLPMIPFYIYY SMFGFQRIGDLCWAAGDQQARGFLIGGTSGRTTLNGEGLQHEDGHSHIQSLTIPNCISYD PAYAYEVAVIMHDGLERMYGEKQENVYYYITTLNENYHMPAMPEGAEEGIRKGIYKLETI EGSKGKVQLLGSGSILRHVREAAEILAKDYGVGSDVYSVTSFTELARDGQDCERWNMLHP LETPRVPYIAQVMNDAPAVASTDYMKLFAEQVRTYVPADDYRVLGTDGFGRSDSRENLRH HFEVDASYVVVAALGELAKRGEIDKKVVADAIAKFNIDADKVNPRLA Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| Drugs and Modes of Action | Top | |||||
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| Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
| 1 | Vitamin B1 | Drug Info | Approved | Vitamin B1 deficiency | [2], [3], [4] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Cofactor | [+] 1 Cofactor drugs | + | ||||
| 1 | Vitamin B1 | Drug Info | [1] | |||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Thiamin diphosphate | Ligand Info | |||||
| Structure Description | E. COLI PYRUVATE DEHYDROGENASE | PDB:1L8A | ||||
| Method | X-ray diffraction | Resolution | 1.85 Å | Mutation | No | [5] |
| PDB Sequence |
ISNYINTIPV
65 EEQPEYPGNL75 ELERRIRSAI85 RWNAIMTVLR95 ASKKDLELGG105 HMASFQSSAT 115 IYDVCFNHFF125 RARNEQDGGD135 LVYFQGHISP145 GVYARAFLEG155 RLTQEQLDNF 165 RQEVHGNGLS175 SYPHPKLMPE185 FWQFPTVSMG195 LGPIGAIYQA205 KFLKYLEHRG 215 LKDTSKQTVY225 AFLGDGEMDE235 PESKGAITIA245 TREKLDNLVF255 VINCNLQRLD 265 GPVTGNGKII275 NELEGIFEGA285 GWNVIKVMWG295 SRWDELLRKD305 TSGKLIQLMN 315 ETVDGDYQTF325 KSKDGAYVRE335 HFFGKYPETA345 ALVADWTDEQ355 IWALNRGGHD 365 PKKIYAAFKK375 AQETKGKATV385 ILAHTIKGYG395 MGDAAMDGVR418 HIRDRFNVPV 428 SDADIEKLPY438 ITFPEGSEEH448 TYLHAQRQKL458 HGYLPSRQPN468 FTEKLELPSL 478 QDFGALLEEQ488 SKEISTTIAF498 VRALNVMLKN508 KSIKDRLVPI518 IADEARTFGM 528 EGLFRQIGIY538 SPEDEKGQIL565 QEGINELGAG575 CSWLAAATSY585 STNNLPMIPF 595 YIYYSMFGFQ605 RIGDLCWAAG615 DQQARGFLIG625 GTSGRTTLNG635 EGLQHEDGHS 645 HIQSLTIPNC655 ISYDPAYAYE665 VAVIMHDGLE675 RMYGEKQENV685 YYYITTLNEN 695 YHMPAMPEGA705 EEGIRKGIYK715 LETIEGSKGK725 VQLLGSGSIL735 RHVREAAEIL 745 AKDYGVGSDV755 YSVTSFTELA765 RDGQDCERWN775 MLHPLETPRV785 PYIAQVMNDA 795 PAVASTDYMK805 LFAEQVRTYV815 PADDYRVLGT825 DGFGRSDSRE835 NLRHHFEVDA 845 SYVVVAALGE855 LAKRGEIDKK865 VVADAIAKFN875 IDADKVNPRL885 A |
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: 3-[(4-Amino-2-methylpyrimidin-5-YL)methyl]-2-{(1S)-1-hydroxy-1-[(R)-hydroxy(methoxy)phosphoryl]ethyl}-5-(2-{[(S)-hydroxy(phosphonooxy)phosphoryl]oxy}ethyl)-4-methyl-1,3-thiazol-3-ium | Ligand Info | |||||
| Structure Description | E. coli Pyruvate dehydrogenase E1 component E401K mutant with phosphonolactylthiamin diphosphate | PDB:2QTC | ||||
| Method | X-ray diffraction | Resolution | 1.77 Å | Mutation | Yes | [6] |
| PDB Sequence |
ISNYINTIPV
65 EEQPEYPGNL75 ELERRIRSAI85 RWNAIMTVLR95 ASKKDLELGG105 HMASFQSSAT 115 IYDVCFNHFF125 RARNEQDGGD135 LVYFQGHISP145 GVYARAFLEG155 RLTQEQLDNF 165 RQEVHGNGLS175 SYPHPKLMPE185 FWQFPTVSMG195 LGPIGAIYQA205 KFLKYLEHRG 215 LKDTSKQTVY225 AFLGDGEMDE235 PESKGAITIA245 TREKLDNLVF255 VINCNLQRLD 265 GPVTGNGKII275 NELEGIFEGA285 GWNVIKVMWG295 SRWDELLRKD305 TSGKLIQLMN 315 ETVDGDYQTF325 KSKDGAYVRE335 HFFGKYPETA345 ALVADWTDEQ355 IWALNRGGHD 365 PKKIYAAFKK375 AQETKGKATV385 ILAHTIKGYG395 MGDAAMDGVR418 HIRDRFNVPV 428 SDADIEKLPY438 ITFPEGSEEH448 TYLHAQRQKL458 HGYLPSRQPN468 FTEKLELPSL 478 QDFGALLEEQ488 SKEISTTIAF498 VRALNVMLKN508 KSIKDRLVPI518 IADEARTFGM 528 EGLFRQIGIY538 SPEDEKGQIL565 QEGINELGAG575 CSWLAAATSY585 STNNLPMIPF 595 YIYYSMFGFQ605 RIGDLCWAAG615 DQQARGFLIG625 GTSGRTTLNG635 EGLQHEDGHS 645 HIQSLTIPNC655 ISYDPAYAYE665 VAVIMHDGLE675 RMYGEKQENV685 YYYITTLNEN 695 YHMPAMPEGA705 EEGIRKGIYK715 LETIEGSKGK725 VQLLGSGSIL735 RHVREAAEIL 745 AKDYGVGSDV755 YSVTSFTELA765 RDGQDCERWN775 MLHPLETPRV785 PYIAQVMNDA 795 PAVASTDYMK805 LFAEQVRTYV815 PADDYRVLGT825 DGFGRSDSRE835 NLRHHFEVDA 845 SYVVVAALGE855 LAKRGEIDKK865 VVADAIAKFN875 IDADKVNPRL885 A |
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HIS106
2.564
SER109
3.297
SER112
4.851
GLN140
3.237
HIS142
2.926
TYR177
3.570
VAL192
2.862
SER193
3.799
MET194
2.971
GLY229
3.277
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Similarity Proteins
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There is no similarity protein (E value < 0.005) for this target
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| References | Top | |||||
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| REF 1 | Vitamins and cofactors: highlights of ESBOC 2009. Nat Chem Biol. 2009 Aug;5(8):530-3. | |||||
| REF 2 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4629). | |||||
| REF 3 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 4 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 040079. | |||||
| REF 5 | Structure of the pyruvate dehydrogenase multienzyme complex E1 component from Escherichia coli at 1.85 A resolution. Biochemistry. 2002 Apr 23;41(16):5213-21. | |||||
| REF 6 | A dynamic loop at the active center of the Escherichia coli pyruvate dehydrogenase complex E1 component modulates substrate utilization and chemical communication with the E2 component. J Biol Chem. 2007 Sep 21;282(38):28106-16. | |||||
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