Crystal structure of mistletoe lectin I from Viscum album.
The crystal structure of the ribosome-inactivating protein (RIP) mistletoe lectin I (ML-I) from Viscum album has been solved by molecular replacement techniques. The structure has been refined to a crystallographic R-factor of 24.5% using X-ray diffraction data to 2.8 A resolution. The heterodimeric 63-kDa protein consists of a toxic A subunit which exhibits RNA-glycosidase activity and a galactose-specific lectin B subunit. The overall protein fold is similar to that of ricin from Ricinus communis; however, unlike ricin, ML-I is already medically applied as a component of a commercially available misteltoe extract with immunostimulating potency and for the treatment of human cancer. The three-dimensional structure reported here revealed structural details of this pharmaceutically important protein. The comparison to the structure of ricin gives more insights into the functional mechanism of this protein, provides structural details for further protein engineering studies, and may lead to the development of more effective therapeutic RIPs.
Krauspenhaar
R
R
Institute of Physiological Chemistry, University Hospital, c/o DESY, Build. 22a, Notkestrasse 85, Hamburg, 22603, Germany.
Eschenburg
S
S
Perbandt
M
M
Kornilov
V
V
Konareva
N
N
Mikailova
I
I
Stoeva
S
S
Wacker
R
R
Maier
T
T
Singh
T
T
Mikhailov
A
A
Voelter
W
W
Betzel
C
C
D000036:Abrin / Q000737:chemistry; D001665:Binding Sites; D017124:Conserved Sequence; D003460:Crystallization; D018360:Crystallography, X-Ray; D003545:Cysteine / Q000737:chemistry / Q000378:metabolism; D019281:Dimerization; D004220:Disulfides / Q000737:chemistry / Q000378:metabolism; D005690:Galactose / Q000378:metabolism; D006860:Hydrogen Bonding; D014784:Mistletoe / Q000737:chemistry*; D008958:Models, Molecular; D037121:Plant Lectins; D028321:Plant Preparations; D010940:Plant Proteins; D010946:Plants, Medicinal; D017433:Protein Structure, Secondary; D054790:Ribosome Inactivating Proteins, Type 2; D012276:Ricin / Q000737:chemistry; D055672:Static Electricity; D014118:Toxins, Biological / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use
D004220:Disulfides; D037121:Plant Lectins; D028321:Plant Preparations; D010940:Plant Proteins; D054790:Ribosome Inactivating Proteins, Type 2; D014118:Toxins, Biological; C488862:mistletoe lectin I; C009674:ribosome inactivating protein, Viscum; D000036:Abrin; D012276:Ricin; D003545:Cysteine; D005690:Galactose