Enzymes without borders: mobilizing substrates, delivering products.
Many cellular reactions involve both hydrophobic and hydrophilic molecules that reside within the chemically distinct environments defined by the phospholipid-based membranes and the aqueous lumens of cytoplasm and organelles. Enzymes performing this type of reaction are required to access a lipophilic substrate located in the membranes and to catalyze its reaction with a polar, water-soluble compound. Here, we explore the different binding strategies and chemical tricks that enzymes have developed to overcome this problem. These reactions can be catalyzed by integral membrane proteins that channel a hydrophilic molecule into their active site, as well as by water-soluble enzymes that are able to capture a lipophilic substrate from the phospholipid bilayer. Many chemical and biological aspects of this type of enzymology remain to be investigated and will require the integration of protein chemistry with membrane biology.
Forneris
Federico
F
Department of Genetics and Microbiology, University of Pavia, Via Ferrata 1, 27100 Pavia, Italy.
Mattevi
Andrea
A
D019883:Alkyl and Aryl Transferases / Q000737:chemistry / Q000378:metabolism; D000581:Amidohydrolases / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D020134:Catalytic Domain; D003600:Cytosol / Q000201:enzymology / Q000378:metabolism; D004058:Diffusion; D004798:Enzymes / Q000737:chemistry* / Q000378:metabolism*; D057927:Hydrophobic and Hydrophilic Interactions; D006913:Hydroxysteroid Dehydrogenases / Q000737:chemistry / Q000378:metabolism; D007425:Intracellular Membranes / Q000201:enzymology / Q000378:metabolism*; D008051:Lipid Bilayers / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D045726:Metalloproteases / Q000737:chemistry / Q000378:metabolism; D008956:Models, Chemical; D015388:Organelles / Q000201:enzymology / Q000378:metabolism*; D046928:Peptidoglycan Glycosyltransferase / Q000737:chemistry / Q000378:metabolism; D000099252:Fatty Acid Amide Hydrolases
D019883:Alkyl and Aryl Transferases; D000581:Amidohydrolases; D004798:Enzymes; D006913:Hydroxysteroid Dehydrogenases; D008051:Lipid Bilayers; D008565:Membrane Proteins; D045726:Metalloproteases; D046928:Peptidoglycan Glycosyltransferase; D000099252:Fatty Acid Amide Hydrolases; C019654:alkylglycerone-phosphate synthase