5MLZ

Dolichyl phosphate mannose synthase in complex with GDP and Mg2+

Summary for 5MLZ

• Entry DOI: 10.2210/pdb5mlz/pdb
• Descriptor: Dolichol monophosphate mannose synthase, GUANOSINE-5'-DIPHOSPHATE, MAGNESIUM ION, ... (6 entities in total)
• Functional Keywords: dolichol phosphate mannose synthase, enzyme, integral membrane protein, protein glycosylation, membrane protein
• Biological source: Pyrococcus furiosus (strain ATCC 43587 / DSM 3638 / JCM 8422 / Vc1)
• Total number of polymer chains: 1
• Total formula weight: 44793.58

Authors

Gandini, R.,Reichenbach, T.,Tan, T.C.,Divne, C. (deposition date: 2016-12-08, release date: 2017-08-09, Last modification date: 2024-05-08)

Primary citation

Gandini, R.,Reichenbach, T.,Tan, T.C.,Divne, C.
Structural basis for dolichylphosphate mannose biosynthesis.
Nat Commun, 8:120-120, 2017

PubMed Abstract: Protein glycosylation is a critical protein modification. In biogenic membranes of eukaryotes and archaea, these reactions require activated mannose in the form of the lipid conjugate dolichylphosphate mannose (Dol-P-Man). The membrane protein dolichylphosphate mannose synthase (DPMS) catalyzes the reaction whereby mannose is transferred from GDP-mannose to the dolichol carrier Dol-P, to yield Dol-P-Man. Failure to produce or utilize Dol-P-Man compromises organism viability, and in humans, several mutations in the human dpm1 gene lead to congenital disorders of glycosylation (CDG). Here, we report three high-resolution crystal structures of archaeal DPMS from Pyrococcus furiosus, in complex with nucleotide, donor, and glycolipid product. The structures offer snapshots along the catalytic cycle, and reveal how lipid binding couples to movements of interface helices, metal binding, and acceptor loop dynamics to control critical events leading to Dol-P-Man synthesis. The structures also rationalize the loss of dolichylphosphate mannose synthase function in dpm1-associated CDG.The generation of glycolipid dolichylphosphate mannose (Dol-P-Man) is a critical step for protein glycosylation and GPI anchor synthesis. Here the authors report the structure of dolichylphosphate mannose synthase in complex with bound nucleotide and donor to provide insight into the mechanism of Dol-P-Man synthesis.

PubMed: 28743912
DOI: 10.1038/s41467-017-00187-2

Experimental method

X-RAY DIFFRACTION (2 Å)