Structure of tyrosine aminotransferase from Leishmania infantum. Issue 5 (1st May 2014)

• Record Type: Journal Article
• Authors: Moreno, M. A.; Abramov, A.; Abendroth, J.; Alonso, A.; Zhang, S.; Alcolea, P. J.; Edwards, T.; Lorimer, D.; Myler, P. J.; Larraga, V.
• Is Part Of: Acta crystallographica. Volume 70:Issue 5(2014:May)
• Page Start: 583
• Page End: 587
• Publication Date: 2014-05-01
• Subjects: Crystallography -- Periodicals; Crystals -- Periodicals; 548
• DOI: 10.1107/S2053230X14007845
• Languages: English
• ISSNs: 2053-230X

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <p>The trypanosomatid parasite <italic>Leishmania infantum</italic> is the causative agent of visceral leishmaniasis (VL), which is usually fatal unless treated. VL has an incidence of 0.5 million cases every year and is an important opportunistic co‐infection in HIV/AIDS. Tyrosine aminotransferase (TAT) has an important role in the metabolism of trypanosomatids, catalyzing the first step in the degradation pathway of aromatic amino acids, which are ultimately converted into their corresponding L‐2‐oxoacids. Unlike the enzyme in <italic>Trypanosoma cruzi</italic> and mammals, <italic>L. infantum</italic> TAT (LiTAT) is not able to transaminate ketoglutarate. Here, the structure of LiTAT at 2.35 Å resolution is reported, and it is confirmed that the presence of two <italic>Leishmania</italic>‐specific residues (Gln55 and Asn58) explains, at least in part, this specific reactivity. The difference in substrate specificity between leishmanial and mammalian TAT and the importance of this enzyme in parasite metabolism suggest that it may be a useful target in the development of new drugs against leishmaniasis.</p> </abstract>