Bacterial Aminopeptidases: Properties and Functions
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ELSEVIER FEMS Microbiology Reviews 18(1996) 3 19-344 Downloaded from https://academic.oup.com/femsre/article/18/4/319/529845 by guest on 24 September 2021 Bacterial aminopeptidases: Properties and functions Thierry Gonzales, Janine Robert-Baudouy * Luhorutoire de Ghznttique Mole’culaire des Microorganismes et des Interactions Cellulaires. C.N.R.S. UMR 5577, Institut Natronal des Sciences Applique’eu. B&iment 406. 20 Avenue Albert Einstein. 69621 Villeurbnnne cede.x, France Received 1 November 1995; revised 18 March 1996; accepted 28 March 1996 Abstract Aminopeptidases are exopeptidases that selectively release N-terminal amino acid residues from polypeptides and proteins. Bacteria display several aminopeptidasic activities which may be localised in the cytoplasm, on membranes, associated with the cell envelope or secreted into the extracellular media. Studies on the bacterial aminopeptide system have been carried out over the past three decades and are significant in fundamental and biotechnological domains. At present, about one hundred bacterial aminopeptidases have been purified and biochemically studied. About forty genes encoding aminopeptidases have also been cloned and characterised. Recently, the three-dimensional structure of two aminopeptidases, the methionine aminopeptidase from Escherichiu coli and the leucine aminopeptidase from Aeromorzas proteo/uica, have been elucidated by crystallographic studies. Most of the quoted studies demonstrate that bacterial aminopeptidases generally show Michaelis-Menten kinetics and can be placed into either of two categories based on their substrate specificity: broad or narrow. These enzymes can also be classified by another criterium based on their catalytic mechanism: metallo-, cysteine- and serine-aminopeptidases, the former type being predominant in bacteria. Aminopeptidases play a role in several important physiological processes. It is noteworthy that some of them take part in the catabolism of exogenously supplied peptides and are necessary for the final steps of protein turnover. In addition, they are involved in some specific functions, such as the cleavage of N-terminal methionine from newly synthesised peptide chains (methionine aminopeptidases), the stabilisation of multicopy ColEI based plasmids (aminopeptidase A) and the pyroglutamyl aminopeptidase (Pep) present in many bacteria and responsible for the cleavage of the N-terminal pyroglutamate. Keywords: Aminopeptidase; Classification; Catalytic mechanism; Location; Function Contents 1. Introduction. 320 2. Biochemical properties of bacterial aminopeptidases. ...................................... 320 2.1. Classification ........................................................... 320 2.2.Structure .............................................................. 321 2.2.1. Quatemary structure. .................................................. 321 2.2.2. Crystallographic studies ................................................ 32 1 * Corresponding author. Tel: + 33 72 43 83 31; Fax: + 33 72 43 87 14: E-mail: [email protected] .fr 0168.6445/96/$32.00 Copyright 0 1996 Federation of European Microbiological Societies. Published by Elsevier Science B.V PI/ SOl68-6445(96)00020-4 320 T. Gonzales, J. Robert-Baudouy/FEMS MicrobiologyReviews 18 (1996) 319-344 2.3. Enzymatic mechanisms ..................................................... 326 2.3.1. The metallo-aminopeptidases ............................................. 326 2.3.2. Cysteine and serine aminopeptidases ......................................... 327 2.4. Enzymatic properties ...................................................... 328 2.5. Substrate specificity ....................................................... 328 3. Cellular location and regulation of bacterial aminopeptidases .................... .......... 329 3.1. Cellular location ............................................ .......... 329 3.2. Regulation of enzyme synthesis ................................... .......... 330 Downloaded from https://academic.oup.com/femsre/article/18/4/319/529845 by guest on 24 September 2021 3.2.1. Transcriptional control .................................... .......... 330 3.2.2. Other mechanisms of regulation. .............................. 331 4. Physiological role of bacterial aminopeptidases................... 331 4.1. Utilisation of exogenous peptides as nutrients. ................ 331 4.2, Degradation of intracellular proteins and peptides .............. 332 4.2.1. Protein turnover .............................. 332 4.2.2. The role of peptidases in the degradation of endogenousproteins . 333 4.2.3. Recognition of proteins to be catabolised ............... 333 4.3. Protein maturation ................................. 334 4.4. Other known functions .............................. 335 5. Conclusions............................................................... 335 Acknowledgement............................................................. 336 References . 336 1. Introduction 2. Biochemical properties of bacterial aminopepti- dases Aminopeptidases are enzymes that catalyse the cleavage of amino acid residues at the N-terminal 2. I. Classification position of peptides and proteins. These enzymes are found widely distributed amongst both procaryotic Peptidases, i.e. enzymes that catalyse the degrada- and eucaryotic types. The first studies on bacterial tion of relatively large peptide fragments, may be aminopeptidases, stimulated by both basic and ap- classified into two groups: endopeptidases and ex- plied interests, were carried out over 30 years ago. opeptidases. The first group comprises enzymes that Some bacterial peptidase systems are of considerable cleave peptide links within the polypeptide chain, interest to agro-industries such as the dairy industry whereas the second consists of enzymes that cleave (for reviews see [ 1 -lo]) while others may be studied amino acid residues at the extremities of the in fundamental research (for a review see [l11) or in polypeptide. Enzymes in the latter group may be bacterial taxonomy (for a review see [12]). These either carboxypeptidases, which free an amino acid studies have allowed the characterisation of a wide residue at the C-terminal end of the polypeptide, or number of aminopeptidases at the biochemical, aminopeptidases, which free an amino acid residue at molecular and physiological levels. the N-terminal end of the polypeptide (Fig. 1). The objective of this review is to summarise The properties of the main bacterial aminopepti- current knowledge concerning both the fundamental dases studied to date are summarised in Table 1. In properties of bacterial aminopeptidases and their po- addition, certain enzymes which are not aminopepti- tential physiological functions. dases in the strict sense of the term, such as dipep- T. Gonzales, J. Robert-Baudouy/ FEMS Microbiology Reriews 18 (1996) 319-344 321 buried within the protein structure while also reduc- ing the contact surface with the medium, thus limit- H,N--Xl -x2- x3-x4-x5 -x6-coon ing the quantity of water necessary to stabilise these Fig. I Peptidases classification. Endopeptidases cleave peptidic proteins [ 151. bounds inside polypeptides (1). Exopeptidases cleave residues To date, only two examples of bacterial amino- located at the N-terminal position (2, aminopeptidases) or C- peptidase displaying hetero-multimeric structures are terminal position (3, carboxypeptidases) of polypeptide. known. The 397-kDa aminopeptidase APMy of Mv- coplasma salivarium (Table 1, family 2) is formed Downloaded from https://academic.oup.com/femsre/article/18/4/319/529845 by guest on 24 September 2021 by the association of two monomers of 46 and 50 tidy1 aminopeptidases (which cleave a dipeptide) as kDa [ 161. The API aminopeptidase of Bacillus well as di- and tri-peptidases (which react on di- or stearothermophilus (Table 1, family 31 is a 400-kDa tri-peptides only) have been included. While this enzyme which appeared a priori to be composed of work aims to be as complete as possible, only en- 12 identical sub-units of 36 kDa [ 171. However, zymes on which a minimum number of studies have N-terminal amino acid sequence determination re- been carried out are quoted. vealed the existence of two distinct sub-unit types Different classification systems exist for which share 67% homology [ 181. This high degree of aminopeptidases. The most frequently used classifi- homology would suggest that the two monomer types, cation parameters include substrate specificity, cellu- termed cr and p, are coded for by phylogenetically lar location, catalytic function, requirement for co- related genes. In addition, it was demonstrated that factors and pH optimum [ 13,141. In this biblio- three isoforms of this enzyme exist in vivo, distin- graphic study, bacterial aminopeptidases were guished by different o//3 ratios [ 191, and that both grouped together into families using the following types of sub-unit possess catalytic activity [ 181. Such criteria: substrate specificity; physico-chemical and complexity of structure may be due to the substrate enzymatic properties (catalytic function, molecular specificity of the CYand p sub-units: the (Y sub-unit weight, pH optimum, etc.) and peptide sequence is specific for non-charged amino acids, while the p similarity (where the corresponding genes have been sub-unit preferentially cleaves acid residues [ 181. The charactet-ised and sequenced). Enzymes classed into resulting hetero-multimer therefore possesses a the same family based uniquely on physico-chemical