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From proteins to peptides to amino acids: comparative genomics of enzymes involved in downstream events during cytosoliv protein degradation

Chandu, Dilip and Nandi, Dipankar (2002) From proteins to peptides to amino acids: comparative genomics of enzymes involved in downstream events during cytosoliv protein degradation. In: Applied Genomics and proteomics, 1 (4). pp. 235-252.

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Abstract

The role of protein degradation in various biological functions is well known. Proteins targeted for destruction are initially degraded by well-studied ATP-dependent proteases (eg 268 proteasomes. Clp. Lon etc) in bacteria and eukaryotes. Recent studies have highlighted the role of enzymes (tricorn, tripeptidyl peptidase II, bleomycin hydrolase. thimet oligopeptidase. prolyl oligopeptidase. leucine aminopeptidase and puromycin sensitive aminopeptidase) in the ATP-independence downstream processing of peptides during cytosolic protein degradation. We describe putative sequence-based homologues of these enzymes in representative organisms from different kingdoms and alignment of active sites resides. Homologues of endopeptidases and some oligopeptidases were not identified in most representative organisms, suggesting specificity during the initial steps of bacterial and eukaryotic protein degradation. However, aminopeptidase holologues were readily found in most representative organisms. Thus, specific endoproteases peptidases are required during the proximal steps of protein degradation by different organisms. peptidases involves during the latter steps of downstream processing are similar across different kingdoms. Also, sequence similarity of peptidase homologues from different organisms may not always correlated with conservation of active site resides leg leucine aminopeptidase holologues in Drosophila melanoguster). Finally, fuctionally similar enzymes may be distinct, lacking sequences homology (eg tricon in Thermoplasma acidophilum and tripeptidy peptidase II in mammals). The strategy used in this study may be used to identify and study the role of corresponding peptidase homologues in different organisms. We have reviewed the current literature on enzymes involved in downstream processing of proteins during cytosolic protein degradation and highlight their specialised functions in different organisms. As inhibition of enzymes involved in general protein turnover will be detrimental to cells, a better understanding of peptidases and their specific functions may result in identification of protential therapeutic targets.

Item Type: Journal Article
Additional Information: Copyright of this article belongs to Open Mind Journals Ltd.
Keywords: prtein degradation;cytosol;peptidase;peptide processing;peptidase holologues;peptidase active sites.
Department/Centre: Division of Biological Sciences > Biochemistry
Date Deposited: 07 Jul 2008
Last Modified: 19 Sep 2010 04:46
URI: http://eprints.iisc.ernet.in/id/eprint/14762

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