6Q4Z

Structure of an inactive variant (D94N) of MPT-2, a GDP-Man-dependent mannosyltransferase from Leishmania mexicana, in complex with beta-1,2-mannobiose

Summary for 6Q4Z

• Entry DOI: 10.2210/pdb6q4z/pdb
• Descriptor: LmxM MPT-2 D94N, beta-D-mannopyranose-(1-2)-alpha-D-mannopyranose (3 entities in total)
• Functional Keywords: transferase
• Biological source: Leishmania mexicana MHOM/GT/2001/U1103
• Total number of polymer chains: 2
• Total formula weight: 76869.12

Authors

Sobala, L.F.,Males, A.,Bastidas, L.M.,Ward, T.,Sernee, M.F.,Ralton, J.E.,Nero, T.L.,Kloehn, J.,Viera-Lara, M.,Stanton, L.,Cobbold, S.,Pires, D.E.,Hanssen, E.,Parker, M.W.,Ascher, D.B.,Williams, S.J.,McConville, M.J.,Davies, G.J. (deposition date: 2018-12-06, release date: 2019-09-25, Last modification date: 2024-01-24)

Primary citation

Sernee, M.F.,Ralton, J.E.,Nero, T.L.,Sobala, L.F.,Kloehn, J.,Vieira-Lara, M.A.,Cobbold, S.A.,Stanton, L.,Pires, D.E.V.,Hanssen, E.,Males, A.,Ward, T.,Bastidas, L.M.,van der Peet, P.L.,Parker, M.W.,Ascher, D.B.,Williams, S.J.,Davies, G.J.,McConville, M.J.
A Family of Dual-Activity Glycosyltransferase-Phosphorylases Mediates Mannogen Turnover and Virulence in Leishmania Parasites.
Cell Host Microbe, 26:385-399.e9, 2019

PubMed Abstract: Parasitic protists belonging to the genus Leishmania synthesize the non-canonical carbohydrate reserve, mannogen, which is composed of β-1,2-mannan oligosaccharides. Here, we identify a class of dual-activity mannosyltransferase/phosphorylases (MTPs) that catalyze both the sugar nucleotide-dependent biosynthesis and phosphorolytic turnover of mannogen. Structural and phylogenic analysis shows that while the MTPs are structurally related to bacterial mannan phosphorylases, they constitute a distinct family of glycosyltransferases (GT108) that have likely been acquired by horizontal gene transfer from gram-positive bacteria. The seven MTPs catalyze the constitutive synthesis and turnover of mannogen. This metabolic rheostat protects obligate intracellular parasite stages from nutrient excess, and is essential for thermotolerance and parasite infectivity in the mammalian host. Our results suggest that the acquisition and expansion of the MTP family in Leishmania increased the metabolic flexibility of these protists and contributed to their capacity to colonize new host niches.

PubMed: 31513773
DOI: 10.1016/j.chom.2019.08.009

Experimental method

X-RAY DIFFRACTION (1.55 Å)