title: Lipase engineering: a window into structure-function relationships.
abstract: Utilization of genetic engineering techniques to create novel functional lipases has increased knowledge of structure-function relationships in this important class of enzymes. The examples of engineered lipases presented in this chapter addressed the investigation of domain-specific properties, heparin binding, and subunit orientation. Conclusions reached are credible because the designed lipases retained catalytic activity, implying native, or near-native, conformation. This approach has demonstrated vigor by determining the domain location of several important enzyme functions and by providing the first evidence that LPL subunits are arranged in a head-to-tail orientation. In conjunction with physical techniques, such as crystallography and nuclear magnetic resonance spectroscopy, the engineered lipase approach could reveal new insights into the mechanism by which lipolysis is accomplished. The studies described here represent only the first attempts to explore that subject; more sophisticated lipase engineering will be used in future as a window into structure-function relationships.
authors.affiliation: Lipid Research Laboratory, West Los Angeles VA Medical Center, California 90073, USA.
authors.forename: H
authors.initials: H
authors.lastname: Wong
authors.forename: R C
authors.initials: RC
authors.lastname: Davis
authors.forename: J S
authors.initials: JS
authors.lastname: Hill
authors.forename: D
authors.initials: D
authors.lastname: Yang
authors.forename: M C
authors.initials: MC
authors.lastname: Schotz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015951:Factor Xa / Q000378:metabolism; D006801:Humans; D008049:Lipase / Q000096:biosynthesis / Q000737:chemistry* / Q000378:metabolism*; D008071:Lipoprotein Lipase / Q000096:biosynthesis / Q000737:chemistry* / Q000378:metabolism*; D008099:Liver / Q000201:enzymology; D010179:Pancreas / Q000201:enzymology; D016133:Polymerase Chain Reaction / Q000379:methods; D015202:Protein Engineering / Q000379:methods*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism
chemical_list: D011993:Recombinant Fusion Proteins; D008049:Lipase; D008071:Lipoprotein Lipase; D015951:Factor Xa