6W2L

Crystal structure of human dehydrodolichyl diphosphate synthase (NgBR/DHDDS) in complex with Mg and IPP

Summary for 6W2L

• Entry DOI: 10.2210/pdb6w2l/pdb
• Descriptor: Dehydrodolichyl diphosphate synthase complex subunit DHDDS, Dehydrodolichyl diphosphate synthase complex subunit NUS1, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: cis-prenyltransferase, dehydrodolichyl diphosphate synthase, transferase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 63058.15

Authors

Edani, B.H.,Ha, Y.,Sessa, W.C. (deposition date: 2020-03-06, release date: 2020-08-19, Last modification date: 2023-10-18)

Primary citation

Edani, B.H.,Grabinska, K.A.,Zhang, R.,Park, E.J.,Siciliano, B.,Surmacz, L.,Ha, Y.,Sessa, W.C.
Structural elucidation of thecis-prenyltransferase NgBR/DHDDS complex reveals insights in regulation of protein glycosylation.
Proc.Natl.Acad.Sci.USA, 117:20794-20802, 2020

PubMed Abstract: prenyltransferase (PTase) catalyzes the rate-limiting step in the synthesis of glycosyl carrier lipids required for protein glycosylation in the lumen of endoplasmic reticulum. Here, we report the crystal structure of the human NgBR/DHDDS complex, which represents an atomic resolution structure for any heterodimeric -PTase. The crystal structure sheds light on how NgBR stabilizes DHDDS through dimerization, participates in the enzyme's active site through its C-terminal -RXG- motif, and how phospholipids markedly stimulate -PTase activity. Comparison of NgBR/DHDDS with homodimeric -PTase structures leads to a model where the elongating isoprene chain extends beyond the enzyme's active site tunnel, and an insert within the α3 helix helps to stabilize this energetically unfavorable state to enable long-chain synthesis to occur. These data provide unique insights into how heterodimeric -PTases have evolved from their ancestral, homodimeric forms to fulfill their function in long-chain polyprenol synthesis.

PubMed: 32817466
DOI: 10.1073/pnas.2008381117

Experimental method

X-RAY DIFFRACTION (2.306 Å)