Domain versatility in plant AB-toxins: evidence for a local, pH-dependent rearrangement in the 2gamma lectin site of the mistletoe lectin by applying ligand derivatives and modelling.
Mistletoe lectin is a potent biohazard. Lectin activity in the toxic dimer primarily originates from the 2gamma-subdomain (Tyr-site) of the B-subunit. Crystallographic information on lectin-sugar complexes is available only at acidic pH, where lectin activity is low. Thus, we mapped ligand-binding properties including comparison to ricin's Tyr-site at neutral pH. Using these results and molecular dynamics simulations, a local conformational change was rendered likely. The obtained structural information is valuable for the design of potent inhibitors.
Instituto de Química Física Rocasolano, Consejo Superior de Investigaciones Cientificas, Serrano 119, Madrid, Spain.
Marta
M
Jiménez
Sabine
S
André
Caterina
C
Barillari
Antonio
A
Romero
Didier
D
Rognan
Hans-Joachim
HJ
Gabius
Dolores
D
Solís
D001212:Asialoglycoproteins / Q000737:chemistry; D003461:Crystallography; D060748:Fetuins; D005690:Galactose / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008024:Ligands; D008756:Methylgalactosides / Q000737:chemistry; D008956:Models, Chemical; D037121:Plant Lectins / Q000737:chemistry* / Q000633:toxicity; D017434:Protein Structure, Tertiary; D012276:Ricin / Q000737:chemistry; D014118:Toxins, Biological / Q000737:chemistry* / Q000633:toxicity; D014443:Tyrosine / Q000737:chemistry; D028182:Viscum album / Q000633:toxicity*; D000509:alpha-Fetoproteins / Q000737:chemistry
D001212:Asialoglycoproteins; D060748:Fetuins; D008024:Ligands; D008756:Methylgalactosides; D037121:Plant Lectins; D014118:Toxins, Biological; D000509:alpha-Fetoproteins; C017029:asialofetuin; C031552:methyl beta-galactoside; D014443:Tyrosine; D012276:Ricin; D005690:Galactose