Reaction mechanisms of thiamin diphosphate enzymes: defining states of ionization and tautomerization of the cofactor at individual steps.
We summarize the currently available information regarding the state of ionization and tautomerization of the 4'-aminopyrimidine ring of the thiamine diphosphate on enzymes requiring this coenzyme. This coenzyme forms a series of covalent intermediates with its substrates as an electrophilic catalyst, and the coenzyme itself also carries out intramolecular proton transfers, which is virtually unprecedented in coenzyme chemistry. An understanding of the state of ionization and tautomerization of the 4'-aminopyrimidine ring in each of these intermediates provides important details about proton movements during catalysis. CD spectroscopy, both steady-state and time-resolved, has proved crucial for obtaining this information because no other experimental method has provided such atomic detail so far.
Nemeria
Natalia S
NS
Department of Chemistry, Rutgers, The State University of New Jersey, Newark, NJ, USA. nemeria@rutgers.edu
Chakraborty
Sumit
S
Balakrishnan
Anand
A
Jordan
Frank
F
D000631:Aminopyridines / Q000737:chemistry / Q000378:metabolism; D002384:Catalysis; D002942:Circular Dichroism; D003067:Coenzymes / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D008958:Models, Molecular; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013835:Thiamine Pyrophosphate / Q000737:chemistry* / Q000378:metabolism
D000631:Aminopyridines; D003067:Coenzymes; D013835:Thiamine Pyrophosphate