3OH2

Protein structure of USP from L. major bound to URIDINE-5'-DIPHOSPHATE-GALACTOSE

Summary for 3OH2

• Entry DOI: 10.2210/pdb3oh2/pdb
• Related: 3OGZ 3OH0 3OH1 3OH3 3OH4
• Descriptor: UDP-sugar pyrophosphorylase, GALACTOSE-URIDINE-5'-DIPHOSPHATE, GLYCEROL, ... (4 entities in total)
• Functional Keywords: left handed beta helix, rossmann fold, udp sugar pyrophosphorylase, transferase
• Biological source: Leishmania major
• Total number of polymer chains: 1
• Total formula weight: 71198.33

Authors

Dickmanns, A.,Damerow, S.,Neumann, P.,Schulz, E.-C.,Lamerz, A.,Routier, F.,Ficner, R. (deposition date: 2010-08-17, release date: 2010-11-17, Last modification date: 2023-09-06)

Primary citation

Dickmanns, A.,Damerow, S.,Neumann, P.,Schulz, E.C.,Lamerz, A.C.,Routier, F.H.,Ficner, R.
Structural basis for the broad substrate range of the UDP-sugar pyrophosphorylase from Leishmania major.
J.Mol.Biol., 405:461-478, 2011

PubMed Abstract: Nucleotide sugars and the enzymes that are responsible for their synthesis are indispensable for the production of complex carbohydrates and, thus, for elaboration of a protective cellular coat for many organisms such as the protozoan parasite Leishmania. These activated sugars are synthesized de novo or derived from salvaged monosaccharides. In addition to UDP-glucose (UDP-Glc) pyrophosphorylase, which catalyzes the formation of UDP-Glc from substrates UTP and glucose-1-phosphate, Leishmania major and plants express a UDP-sugar pyrophosphorylase (USP) that exhibits broad substrate specificity in vitro. The enzyme, likely involved in monosaccharide salvage, preferentially generates UDP-Glc and UDP-galactose, but it may also activate other hexose- or pentose-1-phosphates such as galacturonic acid-1-phosphate or arabinose-1-phosphate. In order to gain insight into structural features governing the differences in substrate specificity, we determined the crystal structure of the L. major USP in the APO-, UTP-, and UDP-sugar-bound conformations. The overall tripartite structure of USP exhibits a significant structural homology to other nucleotidyldiphosphate-glucose pyrophosphorylases. The obtained USP structures reveal the structural rearrangements occurring during the stepwise binding process of the substrates. Moreover, the different product complexes explain the broad substrate specificity of USP, which is enabled by structural changes in the sugar binding region of the active site.

PubMed: 21073876
DOI: 10.1016/j.jmb.2010.10.057

Experimental method

X-RAY DIFFRACTION (2.14 Å)