Molecule Information

General Information of the Molecule (ID: Mol02075)

• Name: NADH dehydrogenase [ubiquinone] flavoprotein 1 (TbAT1) ,Trypanosoma brucei
• Synonyms: Tb927.5.450b
• Molecule Type: Protein
• Gene Name: TbAT1
• Sequence:
  MLRRVGFLSATGSLLQAAASQQPPTQQEQRVHGGLKDQDRIFVNLYQDFGTDIDSAERRG
  DWYRTRDLLLKGHDWVINEIKASGLRGRGGAGFPSGLKWSFMPKSKPDGRPSYIVVNGDE
  SEPGTCKDREIMRHEPHKLVEGALIAGFAMRARYGYIYIRGEFYNEWRAVDQAIKEAYAR
  GYLGRNACGSGYDFDLYTYCGAGAYICGEETAMISSIEGGPGKPRLKPPFPANVGLYGCP
  TTVTNVETVSVSPTILRRGPSWFNSFGRRNNAGVKLFCICGHVNRPCTVEEEMSIPLRDL
  IERHAGGVRGGWDNLLAVIPGGSSCPLIPKSICDNVLMDFDALKEAQTGLGTAAVIVMDK
  STDLIAAIHRLSMFYAHESCGQCTPCREGSPWLEKMMQRFVHGNARMEEVGTMLDVSKQL
  EGRTICALATAAAWPVQGLARHFTPLLQERIEKYWEANPHWGKSGSPWRRWKTHRYYAMQ
  KGEKLNWDGKIVRNWN
• Function: Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor. Essential for the catalytic activity and assembly of complex I.
• Uniprot ID: B2ZWD5_TRYB2

Kingdom: N.A.
Phylum: Euglenozoa
Class: Kinetoplastea
Order: Trypanosomatida
Family: Trypanosomatidae
Genus: Trypanosoma
Species: Trypanosoma brucei

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Pentamidine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: African trypanosomiasis [1]

• Resistant Disease: African trypanosomiasis [ICD-11: 1F51.0]
• Resistant Drug: Pentamidine
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Trypanosoma brucei strain; 5691
• Mechanism Description: Reduced uptake and cross-resistance were apparently explained by the findings that melamine-based arsenicals and diamidines are imported into trypanosomes by the same transporter, and that this transporter is defective in drug-resistant cells. The transporter was called P2 (purine transporter 2) as its physiological substrates are adenine and adenosine, both of which compete with melarsoprol for uptake and can protect trypanosomes from melarsoprol-induced lysis.

Investigative Drug(s) 1 drug(s) in total

Melamine-based arsenicals

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: African trypanosomiasis [1]

• Resistant Disease: African trypanosomiasis [ICD-11: 1F51.0]
• Resistant Drug: Melamine-based arsenicals
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Trypanosoma brucei strain; 5691
• Mechanism Description: Reduced uptake and cross-resistance were apparently explained by the findings that melamine-based arsenicals and diamidines are imported into trypanosomes by the same transporter, and that this transporter is defective in drug-resistant cells. The transporter was called P2 (purine transporter 2) as its physiological substrates are adenine and adenosine, both of which compete with melarsoprol for uptake and can protect trypanosomes from melarsoprol-induced lysis.

References

• Ref 1: Drug resistance in African trypanosomiasis: the melarsoprol and pentamidine story .Trends Parasitol. 2013 Mar;29(3):110-8. doi: 10.1016/j.pt.2012.12.005. Epub 2013 Jan 30. 10.1016/j.pt.2012.12.005