The alpha/beta hydrolase fold.
We have identified a new protein fold--the alpha/beta hydrolase fold--that is common to several hydrolytic enzymes of widely differing phylogenetic origin and catalytic function. The core of each enzyme is similar: an alpha/beta sheet, not barrel, of eight beta-sheets connected by alpha-helices. These enzymes have diverged from a common ancestor so as to preserve the arrangement of the catalytic residues, not the binding site. They all have a catalytic triad, the elements of which are borne on loops which are the best-conserved structural features in the fold. Only the histidine in the nucleophile-histidine-acid catalytic triad is completely conserved, with the nucleophile and acid loops accommodating more than one type of amino acid. The unique topological and sequence arrangement of the triad residues produces a catalytic triad which is, in a sense, a mirror-image of the serine protease catalytic triad. There are now four groups of enzymes which contain catalytic triads and which are related by convergent evolution towards a stable, useful active site: the eukaryotic serine proteases, the cysteine proteases, subtilisins and the alpha/beta hydrolase fold enzymes.
Ollis
D L
DL
Research School of Chemistry, Australian National University, Canberra.
Cheah
E
E
Cygler
M
M
Dijkstra
B
B
Frolow
F
F
Franken
S M
SM
Harel
M
M
Remington
S J
SJ
Silman
I
I
Schrag
J
J
D000110:Acetylcholinesterase / Q000737:chemistry; D000595:Amino Acid Sequence; D001665:Binding Sites; D005075:Biological Evolution; D002265:Carboxylic Ester Hydrolases / Q000737:chemistry; D002268:Carboxypeptidases / Q000737:chemistry; D002384:Catalysis; D006639:Histidine / Q000737:chemistry; D006867:Hydrolases / Q000737:chemistry* / Q000378:metabolism; D008049:Lipase / Q000737:chemistry; D008969:Molecular Sequence Data; D011487:Protein Conformation; D014961:X-Ray Diffraction
D006639:Histidine; D006867:Hydrolases; D002265:Carboxylic Ester Hydrolases; D008049:Lipase; C046130:carboxymethylenebutenolidase; D000110:Acetylcholinesterase; D002268:Carboxypeptidases