title: GDSL family of serine esterases/lipases.
abstract: GDSL esterases and lipases are hydrolytic enzymes with multifunctional properties such as broad substrate specificity and regiospecificity. They have potential for use in the hydrolysis and synthesis of important ester compounds of pharmaceutical, food, biochemical, and biological interests. This new subclass of lipolytic enzymes possesses a distinct GDSL sequence motif different from the GxSxG motif found in many lipases. Unlike the common lipases, GDSL enzymes do not have the so called nucleophile elbow. Studies show that GDSL hydrolases have a flexible active site that appears to change conformation with the presence and binding of the different substrates, much like the induced fit mechanism proposed by Koshland. Some of the GDSL enzymes have thioesterase, protease, arylesterase, and lysophospholipase activity, yet they appear to be the same protein with similar molecular weight ( approximately 22-60 kDa for most esterases), although some have multiple glycosylation sites with higher apparent molecular weight. GDSL enzymes have five consensus sequence (I-V) and four invariant important catalytic residues Ser, Gly, Asn, and His in blocks I, II, III, and V, respectively. The oxyanion structure led to a new designation of these enzymes as SGNH-hydrolase superfamily or subfamily. Phylogenetic analysis revealed that block IIA which belonged to the SGNH-hydrolases was found only in clade I. Therefore, this family of hydrolases represents a new example of convergent evolution of lipolytic enzymes. These enzymes have little sequence homology to true lipases. Another important differentiating feature of GDSL subfamily of lipolytic enzymes is that the serine-containing motif is closer to the N-terminus unlike other lipases where the GxSxG motif is near the center. Since the first classification of these subclass or subfamily of lipases as GDSL(S) hydrolase, progress has been made in determining the consensus sequence, crystal structure, active site and oxyanion residues, secondary structure, mechanism of catalysis, and understanding the conformational changes. Nevertheless, much still needs to be done to gain better understanding of in vivo biological function, 3-D structure, how this group of enzymes evolved to utilize many different substrates, and the mechanism of reactions. Protein engineering is needed to improve the substrate specificity, enantioselectivity, specific activity, thermostability, and heterologous expression in other hosts (especially food grade microorganisms) leading to eventual large scale production and applications. We hope that this review will rekindle interest among researchers and the industry to study and find uses for these unique enzymes.
authors.affiliation: Department of Food Science and Technology, University of Georgia, Athens, GA 30602-7610, USA.
authors.forename: Casimir C
authors.initials: CC
authors.lastname: Akoh
authors.forename: Guan-Chiun
authors.initials: GC
authors.lastname: Lee
authors.forename: Yen-Chywan
authors.initials: YC
authors.lastname: Liaw
authors.forename: Tai-Huang
authors.initials: TH
authors.lastname: Huang
authors.forename: Jei-Fu
authors.initials: JF
authors.lastname: Shaw
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002265:Carboxylic Ester Hydrolases / Q000235:genetics; D020134:Catalytic Domain; D016384:Consensus Sequence; D004950:Esterases / Q000145:classification* / Q000235:genetics; D005818:Genetic Engineering; D008049:Lipase / Q000145:classification* / Q000235:genetics; D008969:Molecular Sequence Data; D011487:Protein Conformation; D016415:Sequence Alignment
chemical_list: D004950:Esterases; C022635:serine esterase; D002265:Carboxylic Ester Hydrolases; C019734:arylesterase; D008049:Lipase