Genome location: Pf3D7_13_v3:1,040,006..1,042,682(+)
Genome classification: Core
Product Description: L-lactate dehydrogenase
SignalP Peptide: N/A
# Transmembrane Domains: 1
EC Numbers: 1.1.1.27 (L-lactate dehydrogenase);1.1.1.37 (Malate dehydrogenase)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0009986 | cell surface |
| Component | GO:0005737 | cytoplasm |
| Component | GO:0005829 | cytosol |
| Component | GO:1903561 | extracellular vesicle |
| Component | GO:0020020 | food vacuole |
| Component | GO:0005622 | intracellular |
| Component | GO:0005739 | mitochondrion |
| Component | GO:0005634 | nucleus |
| Function | GO:0004459 | L-lactate dehydrogenase activity |
| Function | GO:0030060 | L-malate dehydrogenase activity |
| Function | GO:0003723 | RNA binding |
| Function | GO:0005515 | protein binding |
| Process | GO:0006096 | glycolytic process |
Expression by stage (LR - Le Roch et al., and MCA - Malaria Cell Atlas):
| Stage | LR class | MCA mean | MCA prop. zeros |
|---|---|---|---|
| Sporozoite | expressed | N/A | N/A |
| Ring | expressed | 0.46 | 0.79 |
| Trophozoite | expressed | 1.16 | 0.43 |
| Schizont | expressed | 0.16 | 0.90 |
| Gametocyte | expressed | 0.25 | 0.85 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1324900
Resistome Missense Mutations: None
Resistome Compounds with Missense Mutations: None
Resistome # Samples with Disruptive Mutations: 0 (0 missense, 0 "interesting" missense)
Zhang Phenotype: Non - Mutable in CDS
MIS: 0.159 | MFS: -2.887 | #Insertions: 0
PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_1340100)
RMgmDB ABS Phenotype: Different from wild type (Pb ortholog: PY17X_1344800)
Modification: Tagged | RMgm-1570
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q76NM3
"Best" AlphaFill ligand hit: BCN (bicine, Local RMSD=0.20) with 4B7U (Global RMSD=0.93)
BRENDA EC Inhibitors:
Orthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| P40926 | Malate dehydrogenase, mitochondrial | Homo sapiens | OMA, OrthoDB | CHEMBL427092CHEMBL3359141CHEMBL3359147CHEMBL427092... |
| P07195 | L-lactate dehydrogenase B chain | Homo sapiens | OrthoMCL BLAST | LDHA Inhibitor, 1LDHA Inhibitor, 8CHEMBL3318469CHEMBL4530052... |
| P04642 | L-lactate dehydrogenase A chain | Rattus norvegicus | OrthoMCL BLAST | LDHA Inhibitor, 26LDHA Inhibitor, 27LDHA Inhibitor, 29LDHA Inhibitor, 31... |
| Q27743 | L-lactate dehydrogenase | Plasmodium falciparum | OrthoMCL BLAST | Gossypol (C9)Oxamic acid derivative, 5Oxamic acid derivative, 6Oxamic acid derivative, 7... |
| Q6VVP7 | L-lactate dehydrogenase | Plasmodium falciparum | OrthoMCL BLAST | Gossypol (C9)Oxamic acid derivative, 5Oxamic acid derivative, 7 |
| P06151 | L-lactate dehydrogenase A chain | OrthoMCL BLAST | CHEMBL4081890CHEMBL4864519CHEMBL4873879CHEMBL4855986... | |
| E1BNS9 | L-lactate dehydrogenase | Bos taurus | OrthoMCL BLAST | Gossypol (C9) |
| P16125 | L-lactate dehydrogenase B chain | OrthoMCL BLAST | Gossypol (C9) | |
| Q5E9B1 | L-lactate dehydrogenase B chain | Bos taurus | OrthoMCL BLAST | Gossypol (C9) |
| P00338 | L-lactate dehydrogenase A chain | Homo sapiens | OrthoMCL BLAST | CHEMBL3318412CHEMBL3318415CHEMBL3318469CHEMBL3358863... |
| B9UDZ5 | L-lactate dehydrogenase | Plasmodium falciparum | OrthoMCL BLAST | Gossypol (C9) |
Ortholog Group (OrthoMCL): OG6_100601
Most Similar Human Ortholog: Q6ZMR3
TM-align score: 0.91 | RMSD: 2.08
Seq Identity: 0.29 | Length: 307 / 316
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000111716 | lactate dehydrogenase B |
| ENSG00000134333 | lactate dehydrogenase A |
| ENSG00000166796 | lactate dehydrogenase C |
| ENSG00000166800 | lactate dehydrogenase A like 6A |
| ENSG00000285854 | novel transcript |
| ENSG00000288299 | lactate dehydrogenase A |
Protein Length: 316 | Molecular Weight (kDa): 34.108
UniProt ID(s): A0A2S0BC21, A0A2S0BC37, A0A2S0BC44, A0A2S0BC46, A0A2S0BF37, A0A2S0D660, A0A2S0D671, A0A2S0D677, A0A4Y5WWV5, Q71T02, Q76NM3
PDB ID(s): 3ZH2
Isoelectric Point: 7.48
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR001236 | Lactate/malate dehydrogenase, N-terminal |
| InterPro | IPR001557 | L-lactate/malate dehydrogenase |
| InterPro | IPR011275 | Malate dehydrogenase, type 3 |
| InterPro | IPR015955 | Lactate dehydrogenase/glycoside hydrolase, family 4, C-terminal |
| InterPro | IPR022383 | Lactate/malate dehydrogenase, C-terminal |
| InterPro | IPR036291 | NAD(P)-binding domain superfamily |
| PFam | PF00056 | Lactate/malate dehydrogenase, N-terminal |
| PFam | PF02866 | Lactate/malate dehydrogenase, C-terminal |
| Superfamily | SSF51735 | NAD(P)-binding domain superfamily |
| Superfamily | SSF56327 | Lactate dehydrogenase/glycoside hydrolase, family 4, C-terminal |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 1 | 10 | 4 | 14 |
| disruptive | 1 | 6 | 3 | 10 |
| missense | 1 | 3 | 3 | 10 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 1 | 21 | 10 | 11 |
| disruptive | 1 | 14 | 8 | 32 |
| missense | 1 | 9 | 8 | 25 |
PlasmoDB Total SNPs: 60
Non-coding: 56 | Synonymous: 3 | Nonsynonymous: 1 | Stop Codon: 0
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 21136929 | Food vacuole proteome of the malarial parasite Plasmodium falciparum. | Lamarque M, Tastet C, ..., Dubremetz JF | 10.1002/prca.200700112 |
| 24043813 | Structural basis for discriminatory recognition of Plasmodium lactatedehydrogenase by a DNA aptamer. | Cheung YW, Kwok J, ..., Tanner JA | 10.1073/pnas.1309538110 |
| 24494818 | A secretory multifunctional serine protease, DegP of Plasmodium falciparum, playsan important role in thermo-oxidative stress, parasite growth and development. | Sharma S, Jadli M, ..., Malhotra P | 10.1111/febs.12732 |
| 27128092 | Interrogating the Plasmodium Sporozoite Surface: Identification ofSurface-Exposed Proteins and Demonstration of Glycosylation on CSP and TRAP byMass Spectrometry-Based Proteomics. | Swearingen KE, Lindner SE, ..., Sinnis P | 10.1371/journal.ppat.1005606 |
| 27380525 | HRP2 and pLDH-Based Rapid Diagnostic Tests, Expert Microscopy, and PCR forDetection of Malaria Infection during Pregnancy and at Delivery in Areas ofVaried Transmission: A Prospective Cohort Study in Burkina Faso and Uganda. | Kyabayinze DJ, Zongo I, ..., Bell D | 10.1371/journal.pone.0156954 |
| 27503796 | Proteome mapping of Plasmodium: identification of the P. yoelii remodellome. | Siau A, Huang X, ..., Preiser PR | 10.1038/srep31055 |
| 28944300 | Proteomic analysis of extracellular vesicles from a Plasmodium falciparum Kenyanclinical isolate defines a core parasite secretome. | Abdi A, Yu L, ..., Rayner J | 10.12688/wellcomeopenres.11910.2 |
| 30379851 | Identification of Plasmodium falciparum nuclear proteins by mass spectrometry andproposed protein annotation. | Briquet S, Ourimi A, ..., Vaquero C | 10.1371/journal.pone.0205596 |
| 30911042 | Extracellular vesicles carrying lactate dehydrogenase induce suicide in increasedpopulation density of Plasmodium falciparum in vitro. | Correa R, Coronado L, ..., Spadafora C | 10.1038/s41598-019-41697-x |
| 31537845 | The interactome of 2-Cys peroxiredoxins in Plasmodium falciparum. | Brandstaedter C, Delahunty C, ..., Becker K | 10.1038/s41598-019-49841-3 |
| 33906926 | Functional Characterization of the m(6)A-Dependent Translational Modulator PfYTH | Sinha A, Baumgarten S, ..., Scherf A | 10.1128/mBio.00661-21 |
| 34494883 | A Prioritized and Validated Resource of Mitochondrial Proteins in PlasmodiumIdentifies Unique Biology. | van Esveld SL, Meerstein-Kessel L, ..., Huynen MA | 10.1128/mSphere.00614-21 |
| 38421701 | Molecular Mechanism of SOX18 in Lipopolysaccharide-Induced Injury of HumanUmbilical Vein Endothelial Cells | Luo J, Fang H, ..., Jiang R | 10.1615/CritRevImmunol.2023050792 |
| 38423905 | Structures, physical properties and antibacterial activity of silvernanoparticles of Lactiplantibacillus plantarum exopolysaccharide | Zang W, Cao H, Ge J, Zhao D | 10.1016/j.ijbiomac.2024.130083 |