Target Information
| Target General Information | Top | |||||
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| Target ID |
T15053
(Former ID: TTDI00006)
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| Target Name |
Lactate dehydrogenase A (LDHA)
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| Synonyms |
Renal carcinoma antigen NYREN59; Renal carcinoma antigen NY-REN-59; PIG19; Llactate dehydrogenase A chain; LDHM; LDH-M; LDH-A; LDH muscle subunit; L-lactate dehydrogenase A chain; Cell proliferationinducing gene 19 protein; Cell proliferation-inducing gene 19 protein
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| Gene Name |
LDHA
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
Cadherin binding, L-lactate dehydrogenase activity, glycolytic process, pyruvate metabolic process, substantia nigra development.
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| BioChemical Class |
CH-OH donor oxidoreductase
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| UniProt ID | ||||||
| EC Number |
EC 1.1.1.27
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| Sequence |
MATLKDQLIYNLLKEEQTPQNKITVVGVGAVGMACAISILMKDLADELALVDVIEDKLKG
EMMDLQHGSLFLRTPKIVSGKDYNVTANSKLVIITAGARQQEGESRLNLVQRNVNIFKFI IPNVVKYSPNCKLLIVSNPVDILTYVAWKISGFPKNRVIGSGCNLDSARFRYLMGERLGV HPLSCHGWVLGEHGDSSVPVWSGMNVAGVSLKTLHPDLGTDKDKEQWKEVHKQVVESAYE VIKLKGYTSWAIGLSVADLAESIMKNLRRVHPVSTMIKGLYGIKDDVFLSVPCILGQNGI SDLVKVTLTSEEEARLKKSADTLWGIQKELQF Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| ADReCS ID | BADD_A02053 ; BADD_A03025 ; BADD_A05924 ; BADD_A06440 ; BADD_A08298 | |||||
| HIT2.0 ID | T55Z0P | |||||
| 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: NADH | Ligand Info | |||||
| Structure Description | Crystal Structure of Lactate Dehydrogenase A in complex with inhibitor compound 29 and NADH | PDB:5W8K | ||||
| Method | X-ray diffraction | Resolution | 1.60 Å | Mutation | No | [2] |
| PDB Sequence |
ATLKDQLIYN
10 LLKEQTPQNK21 ITVVGVGAVG31 MACAISILMK41 DLADELALVD51 VIEDKLKGEM 61 MDLQHGSLFL71 RTPKIVSGKD81 YNVTANSKLV91 IITAGARLNL108 VQRNVNIFKF 118 IIPNVVKYSP128 NCKLLIVSNP138 VDILTYVAWK148 ISGFPKNRVI158 GSGCNLDSAR 168 FRYLMGERLG178 VHPLSCHGWV188 LGEHGDSSVP198 VWSGMNVAGV208 SLKTLHPDLG 218 TDKDKEQWKE228 VHKQVVESAY238 EVIKLKGYTS248 WAIGLSVADL258 AESIMKNLRR 268 VHPVSTMIKG278 LYGIKDDVFL288 SVPCILGQNG298 ISDLVKVTLT308 SEEEARLKKS 318 ADTLWGIQKE328 LQF
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VAL25
3.803
GLY26
3.927
VAL27
4.110
GLY28
3.247
ALA29
3.234
VAL30
2.956
GLY31
4.299
VAL50
4.515
ASP51
2.708
VAL52
3.452
ILE53
3.311
LYS56
2.810
TYR82
4.195
THR94
3.119
ALA95
3.321
GLY96
3.276
ALA97
2.999
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Nicotinamide-Adenine-Dinucleotide | Ligand Info | |||||
| Structure Description | Lactate Dehydrogenase in complex with inhibitor (R)-3-((2-chlorophenyl)thio)-6-(3-((4-fluorophenyl)amino)phenyl)-4-hydroxy-6-(thiophen-3-yl)-5,6-dihydro-2H-pyran-2-one | PDB:6BB0 | ||||
| Method | X-ray diffraction | Resolution | 1.95 Å | Mutation | No | [3] |
| PDB Sequence |
ATLKDQLIYN
10 LLKEEQTPQN20 KITVVGVGAV30 GMACAISILM40 KDLADELALV50 DVIEDKLKGE 60 MMDLQHGSLF70 LRTPKIVSGK80 DYNVTANSKL90 VIITAGALNL108 VQRNVNIFKF 118 IIPNVVKYSP128 NCKLLIVSNP138 VDILTYVAWK148 ISGFPKNRVI158 GSGCNLDSAR 168 FRYLMGERLG178 VHPLSCHGWV188 LGEHGDSSVP198 VWSGMNVAGV208 SLKTLHPDLG 218 TDKDKEQWKE228 VHKQVVESAY238 EVIKLKGYTS248 WAIGLSVADL258 AESIMKNLRR 268 VHPVSTMIKG278 LYGIKDDVFL288 SVPCILGQNG298 ISDLVKVTLT308 SEEEARLKKS 318 ADTLWGIQKE328 LQF
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VAL25
3.842
GLY26
4.148
VAL27
4.038
GLY28
3.361
ALA29
3.245
VAL30
3.011
GLY31
4.311
VAL50
4.547
ASP51
2.555
VAL52
3.690
ILE53
3.366
TYR82
4.254
THR94
3.143
ALA95
3.380
GLY96
3.505
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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 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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| Glycolysis / Gluconeogenesis | hsa00010 | Affiliated Target |
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| Class: Metabolism => Carbohydrate metabolism | Pathway Hierarchy | ||
| Cysteine and methionine metabolism | hsa00270 | Affiliated Target |
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| Class: Metabolism => Amino acid metabolism | Pathway Hierarchy | ||
| Pyruvate metabolism | hsa00620 | Affiliated Target |
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| Class: Metabolism => Carbohydrate metabolism | Pathway Hierarchy | ||
| Propanoate metabolism | hsa00640 | Affiliated Target |
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| Class: Metabolism => Carbohydrate metabolism | Pathway Hierarchy | ||
| HIF-1 signaling pathway | hsa04066 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Glucagon signaling pathway | hsa04922 | Affiliated Target |
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| Class: Organismal Systems => Endocrine system | Pathway Hierarchy | ||
| Click to Show/Hide the Information of Affiliated Human Pathways | |||
| Degree | 7 | Degree centrality | 7.52E-04 | Betweenness centrality | 7.97E-04 |
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| Closeness centrality | 2.20E-01 | Radiality | 1.39E+01 | Clustering coefficient | 2.38E-01 |
| Neighborhood connectivity | 2.06E+01 | Topological coefficient | 1.82E-01 | Eccentricity | 11 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
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| Target-regulating microRNAs | ||||||
| Target-interacting Proteins | ||||||
| References | Top | |||||
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| REF 1 | Lactate dehydrogenase A in cancer: a promising target for diagnosis and therapy. IUBMB Life. 2013 Nov;65(11):904-10. | |||||
| REF 2 | Discovery and Optimization of Potent, Cell-Active Pyrazole-Based Inhibitors of Lactate Dehydrogenase (LDH). J Med Chem. 2017 Nov 22;60(22):9184-9204. | |||||
| REF 3 | Structure-guided optimization and in vivo activities of hydroxylactone and hydroxylactam Inhibitors of Human Lactate Dehydrogenase | |||||
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