Evolutionary Lines of Cysteine Peptidases

Abstract The proteolytic enzymes that depend upon a cysteine residue for activity have come from at least seven different evolutionary origins, each of which has produced a group of cysteine peptidases with distinctive structures and properties. We show here that the characteristic molecular topologies of the peptidases in each evolutionary line can be seen not only in their threedimensional structures, but commonly also in the twodimensional structures. Clan CA contains the families of papain (C1), calpain (C2), streptopain (C10) and the ubiquitinspecific peptidases (C12, C19), as well as many families of viral cysteine endopeptidases. Clan CD contains the families of clostripain (C11), gingipain R (C25), legumain (C13), caspase-1 (C14) and separin (C50). These enzymes have specificities dominated by the interactions of the S1 subsite. Clan CE contains the families of adenain (C5) from adenoviruses, the eukaryotic Ulp1 protease (C48) and the bacterial YopJ proteases (C55). Clan CF contains only pyroglutamyl peptidase I (C15). The picornains (C3) in clan PA have probably evolved from serine peptidases, which still form the majority of enzymes in the clan. The cysteine peptidase activities in clans PB and CH are autolytic only. In conclusion, we suggest that although almost all the cysteine peptidases depend for activity on catalytic dyads of cysteine and histidine, it is worth noting some important differences that they have inherited from their distant ancestral peptidases.

[1]  S. Moore,et al.  On the specificity of streptococcal proteinase. , 1966, The Journal of biological chemistry.

[2]  R. Ménard,et al.  Catalytic mechanism in papain family of cysteine peptidases. , 1994, Methods in enzymology.

[3]  F. Perler,et al.  Protein Splicing of Inteins and Hedgehog Autoproteolysis: Structure, Function, and Evolution , 1998, Cell.

[4]  Neil D. Rawlings,et al.  MEROPS: the protease database , 2002, Nucleic Acids Res..

[5]  R. Huber,et al.  Crystal structure of gingipain R: an Arg‐specific bacterial cysteine proteinase with a caspase‐like fold , 1999, The EMBO journal.

[6]  Kim Nasmyth,et al.  Cleavage of Cohesin by the CD Clan Protease Separin Triggers Anaphase in Yeast , 2000, Cell.

[7]  M. Hochstrasser,et al.  A new protease required for cell-cycle progression in yeast , 1999, Nature.

[8]  J. Tormo,et al.  Structural and biochemical features distinguish the foot-and-mouth disease virus leader proteinase from other papain-like enzymes. , 2000, Journal of molecular biology.

[9]  L. Polgár.  Mechanisms of Protease Action , 1989 .

[10]  R. Fletterick,et al.  Viral cysteine proteases are homologous to the trypsin-like family of serine proteases: structural and functional implications. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[11]  I. Auger,et al.  Molecular modeling and site-directed mutagenesis define the catalytic motif in human gamma -glutamyl hydrolase. , 2000, Journal of Biological Chemistry.

[12]  J. Dixon,et al.  Disruption of signaling by Yersinia effector YopJ, a ubiquitin-like protein protease. , 2000, Science.

[13]  E. Koonin,et al.  Crystal Structure of a Hedgehog Autoprocessing Domain: Homology between Hedgehog and Self-Splicing Proteins , 1997, Cell.

[14]  K. Nasmyth,et al.  Disjunction of Homologous Chromosomes in Meiosis I Depends on Proteolytic Cleavage of the Meiotic Cohesin Rec8 by Separin , 2000, Cell.

[15]  E. Shaw,et al.  The design of peptidyldiazomethane inhibitors to distinguish between the cysteine proteinases calpain II, cathepsin L and cathepsin B. , 1988, The Biochemical journal.

[16]  M. James,et al.  The refined crystal structure of the 3C gene product from hepatitis A virus: specific proteinase activity and RNA recognition , 1997, Journal of virology.

[17]  W. Kabsch,et al.  Dictionary of protein secondary structure: Pattern recognition of hydrogen‐bonded and geometrical features , 1983, Biopolymers.

[18]  I. G. Kamphuis,et al.  Thiol proteases. Comparative studies based on the high-resolution structures of papain and actinidin, and on amino acid sequence information for cathepsins B and H, and stem bromelain. , 1985, Journal of molecular biology.

[19]  鈴木 俊顕.  A new 30-kDa ubiquitin-related SUMO-1 hydrolase from bovine brain , 2000 .

[20]  I. Auger,et al.  Molecular Modeling and Site-directed Mutagenesis Define the Catalytic Motif in Human γ-Glutamyl Hydrolase* , 2000, The Journal of Biological Chemistry.

[21]  J. Mankovich,et al.  Crystal structure of the cysteine protease interleukin-1β-converting enzyme: A (p20/p10)2 homodimer , 1994, Cell.

[22]  A. Berger,et al.  Mapping the active site of papain with the aid of peptide substrates and inhibitors. , 1970, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[23]  N. Rawlings,et al.  Identification of the active site of legumain links it to caspases, clostripain and gingipains in a new clan of cysteine endopeptidases , 1998, FEBS letters.