The Zn-peptidase superfamily: functional convergence after evolutionary divergence.

Zn-dependent carboxypeptidases (ZnCP) cleave off the C-terminal amino acid residues from proteins and peptides. Here we describe a superfamily that unites classical ZnCP with other enzymes, most of which are known (or likely) to participate in metal-dependent peptide bond cleavage, but not necessarily in polypeptide substrates. It is demonstrated that aspartoacylase (ASP gene) and succinylglutamate desuccinylase (ASTE gene) are members of the ZnCP family. The Zn-binding site along with the structural core of the protein is shown to be conserved between ZnCP and another large family of hydrolases that includes mostly aminopeptidases (ZnAP). Both families (ZnCP and ZnAP) include not only proteases but also enzymes that perform N-deacylation, and enzymes that catalyze N-desuccinylation of amino acids. This is a result of functional convergence that apparently occurred after the divergence of the two families.

[1]  F. Avilés,et al.  The three‐dimensional structure of human procarboxypeptidase A2. Deciphering the basis of the inhibition, activation and intrinsic activity of the zymogen , 1997, The EMBO journal.

[2]  H. Wiese,et al.  J. Goodisman: “Electrochemistry: Theoretical Foundations”, John Wiley & Sons, Inc., New York, Chichester, Brisbane, Toronto, Singapore 1987. 374 Seiten, Preis: £ 50.45 , 1988 .

[3]  N. Rawlings,et al.  Evolutionary families of metallopeptidases. , 1995, Methods in enzymology.

[4]  R. Kaul,et al.  Cloning of the human aspartoacylase cDNA and a common missense mutation in Canavan disease , 1993, Nature genetics.

[5]  P. Brick,et al.  Crystal structure of carboxypeptidase G2, a bacterial enzyme with applications in cancer therapy. , 1997, Structure.

[6]  W. Lipscomb,et al.  Mechanism of carboxypeptidase A: hydration of a ketonic substrate analogue. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[7]  R. Russell,et al.  Detection of protein three-dimensional side-chain patterns: new examples of convergent evolution. , 1998, Journal of molecular biology.

[8]  Seledtsov Ia,et al.  [Multiple alignment of biopolymer sequences, based on the search for statistically significant common segments]. , 1995 .

[9]  N. Glansdorff,et al.  Acetylornithine deacetylase, succinyldiaminopimelate desuccinylase and carboxypeptidase G2 are evolutionarily related. , 1992, Gene.

[10]  B. Rost,et al.  Combining evolutionary information and neural networks to predict protein secondary structure , 1994, Proteins.

[11]  L. Fricker,et al.  Cloning and Expression of Human Carboxypeptidase Z, a Novel Metallocarboxypeptidase* , 1997, The Journal of Biological Chemistry.

[12]  V. Stepanov.  [42] Carboxypeptidase T , 1995 .

[13]  K. Takaoka,et al.  A cDNA cloning of human AEBP1 from primary cultured osteoblasts and its expression in a differentiating osteoblastic cell line. , 1996, Biochemical and biophysical research communications.

[14]  S. Bryant,et al.  Threading a database of protein cores , 1995, Proteins.

[15]  L. Reitzer,et al.  Arginine Catabolism and the Arginine Succinyltransferase Pathway in Escherichia coli , 1998, Journal of bacteriology.

[16]  N. Grishin,et al.  Primary structure of carboxypeptidase T: Delineation of functionally relevant features in Zn-carboxypeptidase family , 1992, Journal of protein chemistry.

[17]  C. Sander,et al.  Dali: a network tool for protein structure comparison. , 1995, Trends in biochemical sciences.

[18]  P. Kraulis.  A program to produce both detailed and schematic plots of protein structures , 1991 .

[19]  B Chevrier,et al.  Crystal structure of Aeromonas proteolytica aminopeptidase: a prototypical member of the co-catalytic zinc enzyme family. , 1994, Structure.

[20]  R M Esnouf,et al.  An extensively modified version of MolScript that includes greatly enhanced coloring capabilities. , 1997, Journal of molecular graphics & modelling.

[21]  J. Felsenstein.  Inferring phylogenies from protein sequences by parsimony, distance, and likelihood methods. , 1996, Methods in enzymology.

[22]  E. Koonin,et al.  Eukaryotic transcription regulators derive from ancient enzymatic domains , 1998, Current Biology.

[23]  Y. Itoh.  Cloning and characterization of the aru genes encoding enzymes of the catabolic arginine succinyltransferase pathway in Pseudomonas aeruginosa , 1997, Journal of bacteriology.

[24]  Gapped BLAST and PSI-BLAST: A new , 1997 .

[25]  O. Bogler,et al.  Cloning, characterization, and expression of the dapE gene of Escherichia coli , 1992, Journal of bacteriology.

[26]  J. Ghuysen,et al.  Characterization of the sporulation-related gamma-D-glutamyl-(L)meso-diaminopimelic-acid-hydrolysing peptidase I of Bacillus sphaericus NCTC 9602 as a member of the metallo(zinc) carboxypeptidase A family. Modular design of the protein. , 1993, The Biochemical journal.

[27]  P Willett,et al.  Three‐dimensional structural resemblance between leucine aminopeptidase and carboxypeptidase A revealed by graph‐theoretical techniques , 1992, FEBS letters.

[28]  S F Altschul,et al.  Iterated profile searches with PSI-BLAST--a tool for discovery in protein databases. , 1998, Trends in biochemical sciences.

[29]  W. Rutter,et al.  Role of the prodomain in folding and secretion of rat pancreatic carboxypeptidase A1. , 1996, Biochemistry.

[30]  A. Murzin.  How far divergent evolution goes in proteins. , 1998, Current opinion in structural biology.

[31]  V. Stepanov.  Carboxypeptidase T. , 1995, Methods in enzymology.

[32]  E. Koonin,et al.  Gleaning non-trivial structural, functional and evolutionary information about proteins by iterative database searches. , 1999, Journal of molecular biology.