title: A twisted base? The role of arginine in enzyme-catalyzed proton abstractions.
abstract: Arginine residues are generally considered poor candidates for the role of general bases because they are predominantly protonated at physiological pH. Nonetheless, Arg residues have recently emerged as general bases in several enzymes: IMP dehydrogenase, pectate/pectin lyases, fumarate reductase, and l-aspartate oxidase. The experimental evidence suggesting this mechanistic function is reviewed. Although these enzymes have several different folds and distinct evolutionary origins, a common structural motif is found where the critical Arg residue is solvent accessible and adjacent to carboxylate groups. The chemistry of the guanidine group suggests unique strategies to lower the pK(a) of Arg. Lastly, the presumption that general bases must be predominantly deprotonated is revisited.
authors.affiliation: Department of Biochemistry, Brandeis University, Waltham, MA 02454, USA.
authors.forename: Yollete V
authors.initials: YV
authors.lastname: Guillén Schlippe
authors.forename: Lizbeth
authors.initials: L
authors.lastname: Hedstrom
mesh_terms: D001120:Arginine / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D002384:Catalysis; D004798:Enzymes / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D008958:Models, Molecular; D008961:Models, Structural; D011487:Protein Conformation; D017510:Protein Folding; D011522:Protons; D013379:Substrate Specificity; D013385:Succinate Dehydrogenase / Q000378:metabolism
chemical_list: D004798:Enzymes; D011522:Protons; D001120:Arginine; D013385:Succinate Dehydrogenase