Target Information
| Target General Information | Top | |||||
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| Target ID |
T88285
(Former ID: TTDR01246)
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| Target Name |
Lactoylglutathione lyase (GLO1)
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| Synonyms |
S-D-lactoylglutathione methylglyoxal lyase; Methylglyoxalase; Ketone-aldehyde mutase; Glyoxalase I; GlxI; Glx I; GLO1; Aldoketomutase
Click to Show/Hide
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| Gene Name |
GLO1
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Influenza [ICD-11: 1E30-1E32] | |||||
| Function |
Catalyzes the conversion of hemimercaptal, formed from methylglyoxal and glutathione, to S-lactoylglutathione. Involved in the regulation of TNF-induced transcriptional activity of NF- kappa-B. Required for normal osteoclastogenesis.
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| BioChemical Class |
Carbon-sulfur lyases
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| UniProt ID | ||||||
| EC Number |
EC 4.4.1.5
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| Sequence |
MAEPQPPSGGLTDEAALSCCSDADPSTKDFLLQQTMLRVKDPKKSLDFYTRVLGMTLIQK
CDFPIMKFSLYFLAYEDKNDIPKEKDEKIAWALSRKATLELTHNWGTEDDETQSYHNGNS DPRGFGHIGIAVPDVYSACKRFEELGVKFVKKPDDGKMKGLAFIQDPDGYWIEILNPNKM ATLM Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T27IAF | |||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
| 1 | BAICALEIN | Drug Info | Phase 2 | Influenza virus infection | [2] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Inhibitor | [+] 16 Inhibitor drugs | + | ||||
| 1 | BAICALEIN | Drug Info | [1] | |||
| 2 | NARINGENIN | Drug Info | [1] | |||
| 3 | 2-Sulfhydryl-Ethanol | Drug Info | [3] | |||
| 4 | KAEMPFEROL | Drug Info | [1] | |||
| 5 | PELARGONIDIN CHLORIDE | Drug Info | [4] | |||
| 6 | S-(N-4bromophenyl-N-hydroxycarbamoyl)glutathione | Drug Info | [5] | |||
| 7 | S-(N-4chlorophenyl-N-hydroxycarbamoyl)glutathione | Drug Info | [5] | |||
| 8 | S-(N-butyl-N-hydroxycarbamoyl)glutathione | Drug Info | [5] | |||
| 9 | S-(N-ethyl-N-hydroxycarbamoyl)glutathione | Drug Info | [5] | |||
| 10 | S-(N-heptyl-N-hydroxycarbamoyl)glutathione | Drug Info | [5] | |||
| 11 | S-(N-Hydroxy-N-Iodophenylcarbamoyl)Glutathione | Drug Info | [3] | |||
| 12 | S-(N-methyl-N-hydroxycarbamoyl)glutathione | Drug Info | [5] | |||
| 13 | S-(N-pentyl-N-hydroxycarbamoyl)glutathione | Drug Info | [5] | |||
| 14 | S-(N-propyl-N-hydroxycarbamoyl)glutathione | Drug Info | [5] | |||
| 15 | S-Benzyl-Glutathione | Drug Info | [6] | |||
| 16 | S-p-bromobenzyl glutatione | Drug Info | [7] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Boric acid | Ligand Info | |||||
| Structure Description | human glyoxalase I (with C-ter His tag) in glycerol-bound form | PDB:7WSZ | ||||
| Method | X-ray diffraction | Resolution | 1.52 Å | Mutation | No | [8] |
| PDB Sequence |
GGLTDEAALS
17 CCSDADPSTK27 DFLLQQTMLR37 VKDPKKSLDF47 YTRVLGMTLI57 QKCDFPIMKF 67 SLYFLAYEDK77 NDIPKEKDEK87 IAWALSRKAT97 LELTHNWGTE107 DDETQSYHNG 117 NSDPRGFGHI127 GIAVPDVYSA137 CKRFEELGVK147 FVKKPDDGKM157 KGLAFIQDPD 167 GYWIEILNPN177 KMATLMLEHH187 HHH
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| Ligand Name: S-(N-Hydroxy-N-Iodophenylcarbamoyl)Glutathione | Ligand Info | |||||
| Structure Description | HUMAN GLYOXALASE I COMPLEXED WITH S-(N-HYDROXY-N-P-IODOPHENYLCARBAMOYL) GLUTATHIONE | PDB:1QIN | ||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | Yes | [9] |
| PDB Sequence |
GGLTDEAALS
17 CCSDADPSTK27 DFLLQQTMLR37 VKDPKKSLDF47 YTRVLGMTLI57 QKCDFPIMKF 67 SLYFLAYEDK77 NDIPKEKDEK87 IAWALSRKAT97 LELTHNWGTE107 DDETQSYHNG 117 NSDPRGFGHI127 GIAVPDVYSA137 CKRFEELGVK147 FVKKPDDGKM157 KGLAFIQDPD 167 GYWIEILNPN177 KMATLM
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| 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 Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Tissue Distribution
Human Pathway Affiliation
Biological Network Descriptors
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There is no similarity protein (E value < 0.005) for this target
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Pyruvate metabolism | hsa00620 | Affiliated Target |
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| Class: Metabolism => Carbohydrate metabolism | Pathway Hierarchy | ||
| Degree | 1 | Degree centrality | 1.07E-04 | Betweenness centrality | 0.00E+00 |
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| Closeness centrality | 1.07E-04 | Radiality | 3.98E-03 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 1.00E+00 | Topological coefficient | . | Eccentricity | 1 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| 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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| BioCyc | [+] 1 BioCyc Pathways | + | ||||
| 1 | Methylglyoxal degradation I | |||||
| KEGG Pathway | [+] 1 KEGG Pathways | + | ||||
| 1 | Pyruvate metabolism | |||||
| NetPath Pathway | [+] 1 NetPath Pathways | + | ||||
| 1 | TCR Signaling Pathway | |||||
| Pathwhiz Pathway | [+] 2 Pathwhiz Pathways | + | ||||
| 1 | Pyruvaldehyde Degradation | |||||
| 2 | Pyruvate Metabolism | |||||
| Reactome | [+] 1 Reactome Pathways | + | ||||
| 1 | Pyruvate metabolism | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Structure-activity relationship of human GLO I inhibitory natural flavonoids and their growth inhibitory effects. Bioorg Med Chem. 2008 Apr 1;16(7):3969-75. | |||||
| REF 2 | ClinicalTrials.gov (NCT03830684) A Randomized, Double-blind, Placebo-controlled, Multicenter and Phase IIa Clinical Trial for the Effectiveness and Safety of Baicalein Tablets in the Treatment of Improve Other Aspects of Healthy Adult With Influenza Fever. U.S. National Institutes of Health. | |||||
| REF 3 | DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-41. | |||||
| REF 4 | Delphinidin, a dietary anthocyanidin in berry fruits, inhibits human glyoxalase I. Bioorg Med Chem. 2010 Oct 1;18(19):7029-33. | |||||
| REF 5 | Role of hydrophobic interactions in binding S-(N-aryl/alkyl-N-hydroxycarbamoyl)glutathiones to the active site of the antitumor target enzyme glyoxalase I. J Med Chem. 2000 Oct 19;43(21):3981-6. | |||||
| REF 6 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
| REF 7 | Inhibition of glyoxalase I: the first low-nanomolar tight-binding inhibitors. J Med Chem. 2009 Aug 13;52(15):4650-6. | |||||
| REF 8 | Crystal structures of human glyoxalase I and its complex with TLSC702 reveal inhibitor binding mode and substrate preference. FEBS Lett. 2022 Jun;596(11):1458-1467. | |||||
| REF 9 | Reaction mechanism of glyoxalase I explored by an X-ray crystallographic analysis of the human enzyme in complex with a transition state analogue. Biochemistry. 1999 Oct 12;38(41):13480-90. | |||||
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