Crystal structures of Trypanosoma cruzi UDP-galactopyranose mutase implicate flexibility of the histidine loop in enzyme activation.

ABSTRACT: Chagas disease is a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi. Here we report crystal structures of the galactofuranose biosynthetic enzyme UDP-galactopyranose mutase (UGM) from T. cruzi, which are the first structures of this enzyme from a protozoan parasite. UGM is an attractive target for drug design because galactofuranose is absent in humans but is an essential component of key glycoproteins and glycolipids in trypanosomatids. Analysis of the enzyme-UDP noncovalent interactions and sequence alignments suggests that substrate recognition is exquisitely conserved among eukaryotic UGMs and distinct from that of bacterial UGMs. This observation has implications for inhibitor design. Activation of the enzyme via reduction of the FAD induces profound conf

SUBMITTER: Dhatwalia R 

PROVIDER: S-EPMC3426654 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature