The kindest cuts of all: crystal structures of Kex2 and furin reveal secrets of precursor processing.
Pro-hormone or pro-protein convertases are a conserved family of eukaryotic serine proteases found in the secretory pathway. These endoproteases mature precursors for peptides and proteins that perform a wide range of physiologically important and clinically relevant functions. The first member of this family to be identified was Kex2 in the yeast Saccharomyces cerevisiae. One mammalian member of this family - furin - is responsible for processing substrates that include insulin pro-receptor, human immunodeficiency virus gp160 glycoprotein, Ebola virus glycoprotein, and anthrax protective antigen. Recent determination of the crystal structures for the catalytic core domains of both Kex2 and furin - the first for any members of this family - provide remarkable insights and a new level of understanding of substrate specificity and catalysis by the pro-protein convertases.
Rockwell
Nathan C
NC
Department of Molecular and Cell Biology, Division of Biochemistry and Molecular Biology, University of California at Berkeley, Room 16, Barker Hall, Berkeley, CA 94720-3202, USA.
Thorner
Jeremy W
JW
D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D002384:Catalysis; D018360:Crystallography, X-Ray; D019286:Endopeptidase K / Q000737:chemistry; D005544:Forecasting; D045683:Furin / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D043484:Proprotein Convertases / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D011498:Protein Precursors / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity; D013381:Subtilisins / Q000737:chemistry; D009626:Terminology as Topic
D011498:Protein Precursors; D029701:Saccharomyces cerevisiae Proteins; D043484:Proprotein Convertases; D013381:Subtilisins; C058751:KEX2 protein, S cerevisiae; D019286:Endopeptidase K; D045683:Furin; D002118:Calcium