Cited by 367Bacterial Genetics and BiotechnologyBiochemical and Structural CharacterizationEnzyme Structure and Function

Evolutionary history, structural features and biochemical diversity of the NlpC/P60 superfamily of enzymes

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Anantharaman, Vivek, Aravind, L·2003·Genome Biology

Abstract

BACKGROUND: Peptidoglycan is hydrolyzed by a diverse set of enzymes during bacterial growth, development and cell division. The N1pC/P60 proteins define a family of cell-wall peptidases that are widely represented in various bacterial lineages. Currently characterized members are known to hydrolyze D-gamma-glutamyl-meso-diaminopimelate or N-acetylmuramate-L-alanine linkages. RESULTS: Detailed analysis of the N1pC/P60 peptidases showed that these proteins define a large superfamily encompassing several diverse groups of proteins. In addition to the well characterized P60-like proteins, this superfamily includes the AcmB/LytN and YaeF/YiiX families of bacterial proteins, the amidase domain of bacterial and kinetoplastid glutathionylspermidine synthases (GSPSs), and several proteins from eukaryotes, phages, poxviruses, positive-strand RNA viruses, and certain archaea. The eukaryotic members include lecithin retinol acyltransferase (LRAT), nematode developmental regulator Egl-26, and candidate tumor suppressor H-rev107. These eukaryotic proteins, along with the bacterial YaeF/poxviral G6R family, show a circular permutation of the catalytic domain. We identified three conserved residues, namely a cysteine, a histidine and a polar residue, that are involved in the catalytic activities of this superfamily. Evolutionary analysis of this superfamily shows that it comprises four major families, with diverse domain architectures in each of them. CONCLUSIONS: Several related, but distinct, catalytic activities, such as murein degradation, acyl transfer and amide hydrolysis, have emerged in the N1pC/P60 superfamily. The three conserved catalytic residues of this superfamily are shown to be equivalent to the catalytic triad of the papain-like thiol peptidases. The predicted structural features indicate that the N1pC/P60 enzymes contain a fold similar to the papain-like peptidases, transglutaminases and arylamine acetyltransferases.

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  • LRAT is classified in the NlpC/P60 thiol peptidase superfamily based on its sequence and predicted tertiary structure.

    “On the basis of its amino acid sequence and predicted tertiary structure, LRAT is classified as a member of the NlpC/P60 thiol peptidase protein superfamily (Figure 22).409”

    From Chemistry of the Retinoid (Visual) Cycle (2014) · cites this paper as [409]

  • LRAT belongs to an ancient and diverse group of proteins called N1pC/P60.

    “Despite being evolutionary ‘young’, LRAT belongs to an ancient and diverse group of proteins called N1pC/P60 [107].”

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Research works printed but not linked: 5

  1. [1]1. Moat AG, Foster JW (Eds): Microbial Physiology, 4th edn. New York: John Wiley; 2002.
  2. [30]30. comment reviews reports deposited research interactions information refereed research http://genomebiology.com/2003/4/2/R11 Genome Biology 2003, Volume 4, Issue 2, Article R11 Anantharaman and Aravind R11.11 Genome Biology 2003, 4:R11
  3. [54]54. Verma R, Aravind L, Oania R, McDonald WH, Yates IJ, Koonin EV, Deshaies RJ: Role of Rpn11 metalloprotease in deubiquitina- tion and degradation by the 26S proteasome. Science 2002, 298:611-615.
  4. [69]69. Kraulis PJ: Molscript. J Appl Crystallogr 1991, 24:946-950.
  5. [73]73. Nielsen H, Engelbrecht J, Brunak S, von Heijne G: Identification of prokaryotic and eukaryotic signal peptides and prediction of their cleavage sites. Protein Eng 1997, 10:1-6.

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Authors
Anantharaman, V., & Aravind, L.
Affiliations
National Institutes of Health (US)
Corresponding author
Aravind, L
Venue
Genome Biology
Published
2003-02-03
Volume
4
Issue
2
Pages
R11-R11
ISSN
  • 1465-6906 (ISSN-L)
  • 1474-760X
OpenAlex
W2113183492
Cited by
365
References
73
Citations by year
2026: 9 · 2025: 13 · 2024: 16 · 2023: 13 · 2022: 18 · 2021: 12 · 2020: 21 · 2019: 12 · 2018: 11 · 2017: 9 · 2016: 15 · 2015: 23 · 2014: 17 · 2013: 20 · 2012: 31
FWCI
7.60
Type
journal article
Language
en
Open access
Locations
  • Genome biology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, other-oa)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Structural Characterization
  • Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
Keywords
peptidoglycan hydrolase, circular permutation, conserved catalytic residues, catalytic triad, acyl transfer, amide hydrolysis, LRAT, domain architecture
MeSH terms
Amino Acid Sequence, Bacterial Proteins, Multigene Family, Models, Molecular, Molecular Sequence Data, Peptide Hydrolases, Phylogeny, Sequence Alignment, Sequence Homology, Amino Acid, Evolution, Molecular

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