Structure of the methyltransferase domain from the Modoc virus, a flavivirus with no known vector.
The Modoc virus (MODV) is a flavivirus with no known vector (NKV). Evolutionary studies have shown that the viruses in the MODV group have evolved in association with mammals (bats, rodents) without transmission by an arthropod vector. MODV methyltransferase is the first enzyme from this evolutionary branch to be structurally characterized. The high-resolution structure of the methyltransferase domain of the MODV NS5 protein (MTase(MODV)) was determined. The protein structure was solved in the apo form and in complex with its cofactor S-adenosyl-L-methionine (SAM). Although it belongs to a separate evolutionary branch, MTase(MODV) shares structural characteristics with flaviviral MTases from the other branches. Its capping machinery is a relatively new target in flaviviral drug development and the observed structural conservation between the three flaviviral branches indicates that it may be possible to identify a drug that targets a range of flaviviruses. The structural conservation also supports the choice of MODV as a possible model for flavivirus studies.
Jansson
Anna M
AM
Department of Cell and Molecular Biology, Uppsala University, Biomedical Center, SE 751 24 Uppsala, Sweden.
Jakobsson
Emma
E
Johansson
Patrik
P
Lantez
Violaine
V
Coutard
Bruno
B
de Lamballerie
Xavier
X
Unge
Torsten
T
Jones
T Alwyn
TA
D000818:Animals; D001179:Arthropod Vectors; D002685:Chiroptera; D003460:Crystallization; D018360:Crystallography, X-Ray; D019143:Evolution, Molecular; D005416:Flavivirus / Q000201:enzymology*; D018177:Flavivirus Infections / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000635:transmission; D008780:Methyltransferases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary / Q000235:genetics; D012314:RNA Cap Analogs / Q000627:therapeutic use; D012315:RNA Caps / Q000378:metabolism; D051381:Rats; D012436:S-Adenosylmethionine / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
D046912:Multiprotein Complexes; C096041:NS5 protein, flavivirus; D012314:RNA Cap Analogs; D012315:RNA Caps; D017361:Viral Nonstructural Proteins; D012436:S-Adenosylmethionine; D008780:Methyltransferases