TY - JOUR
T1 - Insights into Allosteric Control of Human Blood Group A and B Glycosyltransferases from Dynamic NMR
AU - Flügge, Friedemann
AU - Peters, Thomas
N1 - Publisher Copyright:
© 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2019/6
Y1 - 2019/6
N2 - Human blood group A and B glycosyltransferases (GTA, GTB) are retaining glycosyltransferases, requiring a catalytic mechanism that conserves the anomeric configuration of the hexopyranose moiety of the donor substrate (UDP-GalNAc, UDP-Gal). Previous studies have shown that GTA and GTB cycle through structurally distinct states during catalysis. Here, we link binding and release of substrates, substrate-analogs, and products to transitions between open, semi-closed, and closed states of the enzymes. Methyl TROSY based titration experiments in combination with zz-exchange experiments uncover dramatic changes of binding kinetics associated with allosteric interactions between donor-type and acceptor-type ligands. Taken together, this highlights how allosteric control of on- and off-rates correlates with conformational changes, driving catalysis to completion.
AB - Human blood group A and B glycosyltransferases (GTA, GTB) are retaining glycosyltransferases, requiring a catalytic mechanism that conserves the anomeric configuration of the hexopyranose moiety of the donor substrate (UDP-GalNAc, UDP-Gal). Previous studies have shown that GTA and GTB cycle through structurally distinct states during catalysis. Here, we link binding and release of substrates, substrate-analogs, and products to transitions between open, semi-closed, and closed states of the enzymes. Methyl TROSY based titration experiments in combination with zz-exchange experiments uncover dramatic changes of binding kinetics associated with allosteric interactions between donor-type and acceptor-type ligands. Taken together, this highlights how allosteric control of on- and off-rates correlates with conformational changes, driving catalysis to completion.
UR - http://www.scopus.com/inward/record.url?scp=85067385250&partnerID=8YFLogxK
U2 - 10.1002/open.201900116
DO - 10.1002/open.201900116
M3 - Journal articles
AN - SCOPUS:85067385250
VL - 8
SP - 760
EP - 769
JO - ChemistryOpen
JF - ChemistryOpen
SN - 2191-1363
IS - 6
ER -