title: Inhibition of fucosyltransferase VII by gallic acid and its derivatives.
abstract: Gallic acid (GA) and several gallate derivatives were identified as inhibitors of fucosyltransferase VII (FucT VII). The inhibition by GA and (-)-epigallocatechin gallate (EGCG) is time-dependent and irreversible. GA and EGCG showed inhibition with IC(50) of 60 and 700 nM, respectively, after pre-incubation with FucT VII in the presence of MnCl(2). Absence of MnCl(2) results in significantly weaker inhibition. Complexation of Mn(2+) with GA, EGCG, and gallate esters was observed. Such complexation, however, is not rate-limiting for the inhibition of FucT VII. Therefore, time-dependent inhibition of fucosyltransferases by GA and EGCG is likely due to the slow inactivation by the inhibitors or Mn-inhibitor complex. Although Mg(2+) or Ca(2+) can replace Mn(2+) for FucT VII activation, none forms a complex with GA or EGCG and hence results in weaker inhibition of FucT VII. GA and EGCG also inhibit FucT IV and alpha2,3-(N)-sialyltransferase in the low micromolar range. The structure-function divergence could be observed, as EGCG, but not GA or gallate esters, inhibits Zn(2+) containing metalloproteases such as TNFalpha convertase, matrix metalloproteases 2 and 7.
authors.affiliation: Department of Immunology, Schering Plough Research Institute, 2015 Galloping Hill Road, K-15-3945, Kenilworth, NJ 07033, USA. xiaoda.niu@spcorp.com
authors.forename: Xiaoda
authors.initials: X
authors.lastname: Niu
authors.forename: Xuedong
authors.initials: X
authors.lastname: Fan
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.forename: Pauline
authors.initials: P
authors.lastname: Ting
authors.forename: Satwant
authors.initials: S
authors.lastname: Narula
authors.forename: Daniel
authors.initials: D
authors.lastname: Lundell
mesh_terms: D002392:Catechin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D004610:Ellagic Acid / Q000378:metabolism / Q000494:pharmacology; D004798:Enzymes / Q000378:metabolism; D005647:Fucosyltransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008345:Manganese / Q000378:metabolism
chemical_list: D004798:Enzymes; D004610:Ellagic Acid; D008345:Manganese; D005707:Gallic Acid; D002392:Catechin; C045651:epigallocatechin gallate; D005647:Fucosyltransferases; C031692:galactoside 3-fucosyltransferase