Systematic comparison of catalytic mechanisms of hydrolysis and transfer reactions classified in the EzCatDB database.
Catalytic mechanisms of 270 enzymes from 131 superfamilies, mainly hydrolases and transferases, were analyzed based on their enzyme structures. A method of systematic comparison and classification of the catalytic reactions was developed. Hydrolysis and transfer reactions closely resemble one another, displaying common mechanisms, single displacement, and double displacement. These displacement mechanisms might be further subclassified according to the type of catalytic factors and nucleophilic substitution involved. Several types of catalytic factors exist: nucleophile, acid, base, stabilizer, modulator, cofactors. Nucleophilic substitution might be categorized as S(N)1/S(N)2 (or dissociative/associative) reactions. The classification indicates that some mechanisms favor particular types of catalytic factors. In hydrolyses of amide bonds and phosphoric ester bonds, mechanisms with single displacement tend to use inorganic cofactors such as zinc and magnesium ions as important catalysts, whereas those with double displacement frequently do not use such cofactors. In contrast, hydrolyses of O-glycoside bond rarely use such cofactors, with one exception. The trypsin-like hydrolytic reaction, which is catalyzed by the classic catalytic triad comprising serine/histidine/aspartate, can be considered as a "super-reaction" because it is observed in at least three nonhomologous enzymes, whereas most reactions are singlets without any nonhomologous enzymes. By dividing complex reactions into several reactions, correlations between active site structures and catalytic functions can be suggested. This classification method is applicable to other reactions such as elimination and isomerization. Furthermore, it will facilitate annotation of enzyme functions from 3D patterns of enzyme active sites. The classification is available at http://mbs.cbrc.jp/EzCatDB/RLCP/index.html.
Nagano
Nozomi
N
Computational Biology Research Center (CBRC), National Institute of Advanced Industrial Science and Technology (AIST), Koto-ku, Tokyo 135-0064, Japan. n.nagano@aist.go.jp
Noguchi
Tamotsu
T
Akiyama
Yutaka
Y
D001665:Binding Sites; D002384:Catalysis; D020134:Catalytic Domain; D030562:Databases, Protein; D006867:Hydrolases / Q000737:chemistry* / Q000378:metabolism; D006868:Hydrolysis; D008024:Ligands; D008954:Models, Biological; D008958:Models, Molecular; D013329:Structure-Activity Relationship; D014166:Transferases / Q000737:chemistry* / Q000378:metabolism
D008024:Ligands; D014166:Transferases; D006867:Hydrolases