Target Information
| Target General Information | Top | |||||
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| Target ID |
T09215
(Former ID: TTDR00619)
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| Target Name |
Mycobacterium Isocitrate lyase (MycB icl)
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| Synonyms |
Isocitratase; Isocitrase; ICL
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| Gene Name |
MycB icl
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
Catalyzes the formation of succinate and glyoxylate from isocitrate, a key step of the glyoxylate cycle. May be involved in the assimilation of one-carbon compounds via the isocitrate lyase- positive serine pathway.
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| BioChemical Class |
Carbon-carbon lyase
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| UniProt ID | ||||||
| EC Number |
EC 4.1.3.1
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| Sequence |
MSVVGTPKSAEQIQQEWDTNPRWKDVTRTYSAEDVVALQGSVVEEHTLARRGAEVLWEQL
HDLEWVNALGALTGNMAVQQVRAGLKAIYLSGWQVAGDANLSGHTYPDQSLYPANSVPQV VRRINNALQRADQIAKIEGDTSVENWLAPIVADGEAGFGGALNVYELQKALIAAGVAGSH WEDQLASEKKCGHLGGKVLIPTQQHIRTLTSARLAADVADVPTVVIARTDAEAATLITSD VDERDQPFITGERTREGFYRTKNGIEPCIARAKAYAPFADLIWMETGTPDLEAARQFSEA VKAEYPDQMLAYNCSPSFNWKKHLDDATIAKFQKELAAMGFKFQFITLAGFHALNYSMFD LAYGYAQNQMSAYVELQEREFAAEERGYTATKHQREVGAGYFDRIATTVDPNSSTTALTG STEEGQFH Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Pyruvic acid | Ligand Info | |||||
| Structure Description | CRYSTAL STRUCTURE OF 3-BROMOPYRUVATE MODIFIED ISOCITRATE LYASE (ICL) FROM MYCOBACTERIUM TUBERCULOSIS | PDB:1F8M | ||||
| Method | X-ray diffraction | Resolution | 1.80 Å | Mutation | No | [1] |
| PDB Sequence |
ASVVGTPKSA
10 EQIQQEWDTN20 PRWKDVTRTY30 SAEDVVALQG40 SVVEEHTLAR50 RGAEVLWEQL 60 HDLEWVNALG70 ALTGNMAVQQ80 VRAGLKAIYL90 SGWQVAGDAN100 LSGHTYPDQS 110 LYPANSVPQV120 VRRINNALQR130 ADQIAKIEGD140 TSVENWLAPI150 VADGEAGFGG 160 ALNVYELQKA170 LIAAGVAGSH180 WEDQLASEKK190 CGHLGGKVLI200 PTQQHIRTLT 210 SARLAADVAD220 VPTVVIARTD230 AEAATLITSD240 VDERDQPFIT250 GERTREGFYR 260 TKNGIEPCIA270 RAKAYAPFAD280 LIWMETGTPD290 LEAARQFSEA300 VKAEYPDQML 310 AYNCSPSFNW320 KKHLDDATIA330 KFQKELAAMG340 FKFQFITLAG350 FHALNYSMFD 360 LAYGYAQNQM370 SAYVELQERE380 FAAEERGYTA390 TKHQREVGAG400 YFDRIATTVD 410 PNSSTTALTG420 STEEGQF
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| Ligand Name: Glyoxalate, Glyoxylate | Ligand Info | |||||
| Structure Description | Intact cis-2,3-epoxysuccinic acid bound to Isocitrate Lyase-1 from Mycobacterium tuberculosis | PDB:6WSI | ||||
| Method | X-ray diffraction | Resolution | 1.75 Å | Mutation | No | [4] |
| PDB Sequence |
MSVVGTPKSA
10 EQIQQEWDTN20 PRWKDVTRTY30 SAEDVVALQG40 SVVEEHTLAR50 RGAEVLWEQL 60 HDLEWVNALG70 ALTGNMAVQQ80 VRAGLKAIYL90 SGWQVAGDAN100 LSGHTYPDQS 110 LYPANSVPQV120 VRRINNALQR130 ADQIAKIEGD140 TSVENWLAPI150 VADGEAGFGG 160 ALNVYELQKA170 LIAAGVAGSH180 WEDQLASEKK190 CGHLGGKVLI200 PTQQHIRTLT 210 SARLAADVAD220 VPTVVIARTD230 AEAATLITSD240 VDERDQPFIT250 GERTREGFYR 260 TKNGIEPCIA270 RAKAYAPFAD280 LIWMETGTPD290 LEAARQFSEA300 VKAEYPDQML 310 AYNCSPSFNW320 KKHLDDATIA330 KFQKELAAMG340 FKFQFITLAG350 FHALNYSMFD 360 LAYGYAQNQM370 SAYVELQERE380 FAAEERGYTA390 TKHQREVGAG400 YFDRIATTVD 410 PNSSTTALTG420 STEEGQF
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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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| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 5 KEGG Pathways | + | ||||
| 1 | Glyoxylate and dicarboxylate metabolism | |||||
| 2 | Metabolic pathways | |||||
| 3 | Biosynthesis of secondary metabolites | |||||
| 4 | Microbial metabolism in diverse environments | |||||
| 5 | Carbon metabolism | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Structure of isocitrate lyase, a persistence factor of Mycobacterium tuberculosis. Nat Struct Biol. 2000 Aug;7(8):663-8. | |||||
| REF 2 | Bromophenols as Candida albicans isocitrate lyase inhibitors. Bioorg Med Chem Lett. 2010 Nov 15;20(22):6644-8. | |||||
| REF 3 | Sesterterpene sulfates as isocitrate lyase inhibitors from tropical sponge Hippospongia sp. Bioorg Med Chem Lett. 2007 May 1;17(9):2483-6. | |||||
| REF 4 | Covalent Inactivation of Mycobacterium tuberculosis Isocitrate Lyase by cis-2,3-Epoxy-Succinic Acid. ACS Chem Biol. 2021 Mar 19;16(3):463-470. | |||||
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