7JID

Crystal structure of the L780 UDP-rhamnose synthase from Acanthamoeba polyphaga mimivirus

Summary for 7JID

• Entry DOI: 10.2210/pdb7jid/pdb
• Descriptor: UDP-L-Rhamnose Synthase, [[(2~{R},3~{S},4~{R},5~{R})-5-[2,4-bis(oxidanylidene)pyrimidin-1-yl]-3,4-bis(oxidanyl)oxolan-2-yl]methoxy-oxidanyl-phosphoryl] [(2~{R},3~{R},4~{R},5~{R},6~{S})-6-methyl-3,4,5-tris(oxidanyl)oxan-2-yl] hydrogen phosphate, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, ... (5 entities in total)
• Functional Keywords: rhamnose, oxidoreductase, mimivirus
• Biological source: Acanthamoeba polyphaga mimivirus (APMV)
• Total number of polymer chains: 2
• Total formula weight: 69533.74

Authors

Bockhaus, N.J.,Ferek, J.D.,Thoden, J.B.,Holden, H.M. (deposition date: 2020-07-23, release date: 2020-08-26, Last modification date: 2023-10-18)

Primary citation

Bockhaus, N.J.,Ferek, J.D.,Thoden, J.B.,Holden, H.M.
The high-resolution structure of a UDP-L-rhamnose synthase from Acanthamoeba polyphaga Mimivirus.
Protein Sci., 29:2164-2174, 2020

PubMed Abstract: For the field of virology, perhaps one of the most paradigm-shifting events so far in the 21st century was the identification of the giant double-stranded DNA virus that infects amoebae. Remarkably, this virus, known as Mimivirus, has a genome that encodes for nearly 1,000 proteins, some of which are involved in the biosynthesis of unusual sugars. Indeed, the virus is coated by a layer of glycosylated fibers that contain d-glucose, N-acetyl-d-glucosamine, l-rhamnose, and 4-amino-4,6-dideoxy-d-glucose. Here we describe a combined structural and enzymological investigation of the protein encoded by the open-reading frame L780, which corresponds to an l-rhamnose synthase. The structure of the L780/NADP /UDP-l-rhamnose ternary complex was determined to 1.45 Å resolution and refined to an overall R-factor of 19.9%. Each subunit of the dimeric protein adopts a bilobal-shaped appearance with the N-terminal domain harboring the dinucleotide-binding site and the C-terminal domain positioning the UDP-sugar into the active site. The overall molecular architecture of L780 places it into the short-chain dehydrogenase/reductase superfamily. Kinetic analyses indicate that the enzyme can function on either UDP- and dTDP-sugars but displays a higher catalytic efficiency with the UDP-linked substrate. Site-directed mutagenesis experiments suggest that both Cys 108 and Lys 175 play key roles in catalysis. This structure represents the first model of a viral UDP-l-rhamnose synthase and provides new details into these fascinating enzymes.

PubMed: 32797646
DOI: 10.1002/pro.3928

Experimental method

X-RAY DIFFRACTION (1.45 Å)