PDBsum entry 2c21

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protein ligands metals Protein-protein interface(s) links
Lyase PDB id
Protein chains
(+ 0 more) 139 a.a. *
MPD ×6
MRD ×2
_NA ×2
_NI ×6
Waters ×839
* Residue conservation analysis
PDB id:
Name: Lyase
Title: Specificity of the trypanothione-dependednt leishmania major glyoxalase i: structure and biochemical comparison with the human enzyme
Structure: Trypanothione-dependent glyoxalase i. Chain: a, b, c, d, e, f. Engineered: yes
Source: Leishmania major. Organism_taxid: 5664. Strain: friedlin a1. Expressed in: escherichia coli. Expression_system_taxid: 469008.
Biol. unit: Dimer (from PDB file)
2.00Å     R-factor:   0.157     R-free:   0.201
Authors: A.Ariza,T.J.Vickers,N.Greig,K.A.Armour,I.M.Eggleston,A.H.Fai C.S.Bond
Key ref: A.Ariza et al. (2006). Specificity of the trypanothione-dependent Leishmania major glyoxalase I: structure and biochemical comparison with the human enzyme. Mol Microbiol, 59, 1239-1248. PubMed id: 16430697
23-Sep-05     Release date:   01-Feb-06    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
Q68RJ8  (Q68RJ8_LEIMA) -  Trypanothione-dependent glyoxalase I
141 a.a.
139 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     metabolic process   1 term 
  Biochemical function     lyase activity     3 terms  


Mol Microbiol 59:1239-1248 (2006)
PubMed id: 16430697  
Specificity of the trypanothione-dependent Leishmania major glyoxalase I: structure and biochemical comparison with the human enzyme.
A.Ariza, T.J.Vickers, N.Greig, K.A.Armour, M.J.Dixon, I.M.Eggleston, A.H.Fairlamb, C.S.Bond.
Trypanothione replaces glutathione in defence against cellular damage caused by oxidants, xenobiotics and methylglyoxal in the trypanosomatid parasites, which cause trypanosomiasis and leishmaniasis. In Leishmania major, the first step in methylglyoxal detoxification is performed by a trypanothione-dependent glyoxalase I (GLO1) containing a nickel cofactor; all other characterized eukaryotic glyoxalases use zinc. In kinetic studies L. major and human enzymes were active with methylglyoxal derivatives of several thiols, but showed opposite substrate selectivities: N1-glutathionylspermidine hemithioacetal is 40-fold better with L. major GLO1, whereas glutathione hemithioacetal is 300-fold better with human GLO1. Similarly, S-4-bromobenzylglutathionylspermidine is a 24-fold more potent linear competitive inhibitor of L. major than human GLO1 (Kis of 0.54 microM and 12.6 microM, respectively), whereas S-4-bromobenzylglutathione is >4000-fold more active against human than L. major GLO1 (Kis of 0.13 microM and >500 microM respectively). The crystal structure of L. major GLO1 reveals differences in active site architecture to both human GLO1 and the nickel-dependent Escherichia coli GLO1, including increased negative charge and hydrophobic character and truncation of a loop that may regulate catalysis in the human enzyme. These differences correlate with the differential binding of glutathione and trypanothione-based substrates, and thus offer a route to the rational design of L. major-specific GLO1 inhibitors.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20512387 G.Colotti, and A.Ilari (2011).
Polyamine metabolism in Leishmania: from arginine to trypanothione.
  Amino Acids, 40, 269-285.  
21310261 S.Wyllie, and A.H.Fairlamb (2011).
Methylglyoxal metabolism in trypanosomes and leishmania.
  Semin Cell Dev Biol, 22, 271-277.  
19731367 L.Shi, P.Gao, X.X.Yan, and D.C.Liang (2009).
Crystal structure of a putative methylmalonyl-coenzyme a epimerase from Thermoanaerobacter tengcongensis at 2.0 A resolution.
  Proteins, 77, 994-999.
PDB code: 3gm5
19101977 X.Wu, P.M.Flatt, H.Xu, and T.Mahmud (2009).
Biosynthetic Gene Cluster of Cetoniacytone A, an Unusual Aminocyclitol from the Endosymbiotic Bacterium Actinomyces sp. Lu 9419.
  Chembiochem, 10, 304-314.  
18588970 F.Irigoín, L.Cibils, M.A.Comini, S.R.Wilkinson, L.Flohé, and R.Radi (2008).
Insights into the redox biology of Trypanosoma cruzi: Trypanothione metabolism and oxidant detoxification.
  Free Radic Biol Med, 45, 733-742.  
  18533363 N.Sukdeo, and J.F.Honek (2008).
Microbial glyoxalase enzymes: metalloenzymes controlling cellular levels of methylglyoxal.
  Drug Metabol Drug Interact, 23, 29-50.  
18959765 S.L.Oza, S.Chen, S.Wyllie, J.K.Coward, and A.H.Fairlamb (2008).
ATP-dependent ligases in trypanothione biosynthesis--kinetics of catalysis and inhibition by phosphinic acid pseudopeptides.
  FEBS J, 275, 5408-5421.  
17664277 M.Deponte, N.Sturm, S.Mittler, M.Harner, H.Mack, and K.Becker (2007).
Allosteric coupling of two different functional active sites in monomeric Plasmodium falciparum glyoxalase I.
  J Biol Chem, 282, 28419-28430.  
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