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.
Jiménez
Marta
M
Instituto de Química Física Rocasolano, Consejo Superior de Investigaciones Cientificas, Serrano 119, Madrid, Spain.
André
Sabine
S
Barillari
Caterina
C
Romero
Antonio
A
Rognan
Didier
D
Gabius
Hans-Joachim
HJ
Solís
Dolores
D
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