Jeremy C. Mottram

Trypanosomiasis and leishmaniasis: biology and control.

Current research into the biology and control of trypanosomiasis and leishmaniasis, Geoff Hide et al Landmarks of trypanosome research, Keith Vickerman Current public health status of the trypanosomiasis and leishmaniasis, David H. Molyneux Sequencing and mapping the African trypanosome genome, Najib M.A. El-Sayed, John E. Donelson The structure and biosynthesis of trypanosomatid glycosylphosphatidylinositols, Michael A.J. Ferguson A genetic analysis of the biosynthetic pathway of the leishmania virulence factor LPG, Salvatore J. Turco, Stephen M. Beverley The biology of antigenic variation in African trypanosomes, J. David Barry The expression sites for variant surface glycoprotein of trypanosome brucei, Piet Borst et al Glycolysis of kinetoplastida, Paul A.M. Michels et al Polyamine metabolism in trypanosomes, Alan H. Fairlamb, Sarah A. Le Quesne Sterol metabolism of leishmania and trypanosomes: potential for chemotherapeutic exploitation, Michael L. Chance, L. John Goad Proteinases of trypanosomes and leishmania, Graham H. Cooms, Jeremy C. Mottram Cell signalling in trypanosomatids, Etienne Pays et al Protein phosphorylation and protein kinases in trypanosomatids, Michael Boshart, Jeremy C. Mottram Chemotherapy of human leishmaniasis and trypanosomiasis, Simon L. Croft et al Drug resistance in trypanosomatids, Carole A. Ross, Diana V. Sutherland The population dynamics and control of zoonotic visceral leishmaniasis, Christopher Dye et al Molecular epidemiology of trypanosomatids, Geoff Hide Evolutionary genetics of trypanosome, leishmania and other microorganisms: epidemiological,taxonomical and medical implications, Michel Tibayrenc Current trends in parasite vector interactions, Susan C. Welburn, Ian Maudin The socio-economic impact of African trypanosomiasis, Andrew James Effects of trypanosomiasis on reproduction in domestic ruminants, Ian A. Jeffcoate, Peter H. Holmes Control strategies for African trypanosomiasis: their sustainability and effectiveness, John Barrett.

The Primitive Protozoon Trichomonas vaginalisContains Two Methionine γ-Lyase Genes That Encode Members of the γ-Family of Pyridoxal 5′-Phosphate-dependent Enzymes

Methionine γ-lyase, the enzyme that catalyzes the breakdown of methionine by an α,γ-elimination reaction and is a member of the γ-family of pyridoxal 5′-phosphate-dependent enzymes, is present in high activity in the primitive protozoan parasite Trichomonas vaginalisbut is absent from mammals. Two genes, mgl1 andmgl2, encoding methionine γ-lyase, have now been isolated from T. vaginalis. They are both single copy, encode predicted proteins (MGL1 and MGL2) of 43 kDa, have 69% sequence identity with each other, and show a high degree of sequence identity to methionine γ-lyase from Pseudomonas putida (44%) and other related pyridoxal 5′-phosphate-dependent enzymes such as human cystathionine γ-lyase (42%) and Escherichia coli cystathionine β-lyase (30%). mgl1 andmgl2 have been expressed in E. coli as a fusion with a six-histidine tag and the recombinant proteins (rMGL1 and rMGL2) purified by metal-chelate affinity chromatography. rMGL1 and rMGL2 were found to have high activity toward methionine (10.4 and 0.67 μmol/min/mg of protein, respectively), homocysteine (370 and 128 μmol/min/mg of protein), cysteine (6.02 and 1.06 μmol/min/mg of protein), and O-acetylserine (3.74 and 1.51 μmol/min/mg of protein), but to be inactive toward cystathionine. Site-directed mutagenesis of an active site cysteine (C113G for MGL1 and C116G for MGL2) reduced the activity of the recombinant enzymes toward both methionine and homocysteine by approximately 80% (rMGL1) and 90% (rMGL2). In contrast, the activity of mutated rMGL2 toward cysteine andO-acetylserine was increased (to 214 and 142%, respectively), whereas that of mutated rMGL1 was reduced to 39 and 49%, respectively. These findings demonstrate the importance of this cysteine residue in the α,β-elimination and α,γ-elimination reactions catalyzed by trichomonad methionine γ-lyase.