TY - JOUR
T1 - How the Same Core Catalytic Machinery Catalyzes 17 Different Reactions
T2 - The Serine-Histidine-Aspartate Catalytic Triad of α/β-Hydrolase Fold Enzymes
AU - Rauwerdink, Alissa
AU - Kazlauskas, Romas J.
N1 - Publisher Copyright:
© 2015 American Chemical Society.
PY - 2015/10/2
Y1 - 2015/10/2
N2 - Enzymes within a family often catalyze different reactions. In some cases, this variety stems from different catalytic machinery, but in other cases, the machinery is identical; nevertheless, the enzymes catalyze different reactions. In this review, we examine the subset of α/β-hydrolase fold enzymes that contain the serine-histidine-aspartate catalytic triad. Despite having the same protein fold and the same core catalytic machinery, these enzymes catalyze 17 different reaction mechanisms. The most common reactions are hydrolysis of C-O, C-N, and C-C bonds (Enzyme Classification (EC) group 3), but other enzymes are oxidoreductases (EC group 1), acyl transferases (EC group 2), lyases (EC group 4), or isomerases (EC group 5). Hydrolysis reactions often follow the canonical esterase mechanism, but eight variations occur in which either the formation or cleavage of the acyl enzyme intermediate differs. The remaining eight mechanisms are lyase-type elimination reactions, which do not have an acyl enzyme intermediate and, in four cases, do not even require the catalytic serine. This diversity of mechanisms from the same catalytic triad stems from the ability of the enzymes to bind different substrates; from the requirements for different chemical steps imposed by these new substrates; and, only in about half of the cases, from additional hydrogen bond partners or additional general acids/bases in the active site. This detailed analysis shows that binding differences and noncatalytic residues create new mechanisms and are essential for understanding and designing efficient enzymes.
AB - Enzymes within a family often catalyze different reactions. In some cases, this variety stems from different catalytic machinery, but in other cases, the machinery is identical; nevertheless, the enzymes catalyze different reactions. In this review, we examine the subset of α/β-hydrolase fold enzymes that contain the serine-histidine-aspartate catalytic triad. Despite having the same protein fold and the same core catalytic machinery, these enzymes catalyze 17 different reaction mechanisms. The most common reactions are hydrolysis of C-O, C-N, and C-C bonds (Enzyme Classification (EC) group 3), but other enzymes are oxidoreductases (EC group 1), acyl transferases (EC group 2), lyases (EC group 4), or isomerases (EC group 5). Hydrolysis reactions often follow the canonical esterase mechanism, but eight variations occur in which either the formation or cleavage of the acyl enzyme intermediate differs. The remaining eight mechanisms are lyase-type elimination reactions, which do not have an acyl enzyme intermediate and, in four cases, do not even require the catalytic serine. This diversity of mechanisms from the same catalytic triad stems from the ability of the enzymes to bind different substrates; from the requirements for different chemical steps imposed by these new substrates; and, only in about half of the cases, from additional hydrogen bond partners or additional general acids/bases in the active site. This detailed analysis shows that binding differences and noncatalytic residues create new mechanisms and are essential for understanding and designing efficient enzymes.
KW - X-ray structures
KW - catalytic triad
KW - divergent evolution
KW - hydrolase
KW - lyase
KW - mechanism
KW - oxyanion hole
UR - http://www.scopus.com/inward/record.url?scp=84943155664&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84943155664&partnerID=8YFLogxK
U2 - 10.1021/acscatal.5b01539
DO - 10.1021/acscatal.5b01539
M3 - Review article
AN - SCOPUS:84943155664
SN - 2155-5435
VL - 5
SP - 6153
EP - 6176
JO - ACS Catalysis
JF - ACS Catalysis
IS - 10
ER -