The PECACE domain: a new family of enzymes with potential peptidoglycan cleavage activity in Gram-positive bacteria.
BACKGROUND
The metabolism of bacterial peptidoglycan is a dynamic process, synthases and cleavage enzymes are functionally coordinated. Lytic Transglycosylase enzymes (LT) are part of multienzyme complexes which regulate bacterial division and elongation. LTs are also involved in peptidoglycan turnover and in macromolecular transport systems. Despite their central importance, no LTs have been identified in the human pathogen Streptococcus pneumoniae. We report the identification of the first putative LT enzyme in S. pneumoniae and discuss its role in pneumococcal peptidoglycan metabolism.


RESULTS
Homology searches of the pneumococcal genome allowed the identification of a new domain putatively involved in peptidoglycan cleavage (PECACE, PEptidoglycan CArbohydrate Cleavage Enzyme). This sequence has been found exclusively in Gram-positive bacteria and gene clusters containing pecace are conserved among Streptococcal species. The PECACE domain is, in some instances, found in association with other domains known to catalyze peptidoglycan hydrolysis.


CONCLUSIONS
A new domain, PECACE, putatively involved in peptidoglycan hydrolysis has been identified in S. pneumoniae. The probable enzymatic activity deduced from the detailed analysis of the amino acid sequence suggests that the PECACE domain may proceed through a LT-type or goose lyzosyme-type cleavage mechanism. The PECACE function may differ largely from the other hydrolases already identified in the pneumococcus: LytA, LytB, LytC, CBPD and PcsB. The multimodular architecture of proteins containing the PECACE domain is another example of the many activities harbored by peptidoglycan hydrolases, which is probably required for the regulation of peptidoglycan metabolism. The release of new bacterial genomes sequences will probably add new members to the five groups identified so far in this work, and new groups could also emerge. Conversely, the functional characterization of the unknown domains mentioned in this work can now become easier, since bacterial peptidoglycan is proposed to be the substrate.
Pagliero
Estelle
E
Laboratoire d'Ingénierie des Macromolécules, Institute de Biologie Structurale, Jean-Pierre Ebel (CEA-CNRS UMR 5075-UJF), 41 Rue Jules Horowitz 38027 Grenoble cedex 1, France. pagliero@ibs.fr
Dideberg
Otto
O
Vernet
Thierry
T
Di Guilmi
Anne Marie
AM
D000595:Amino Acid Sequence; D002384:Catalysis; D002473:Cell Wall; D002794:Choline / Q000737:chemistry; D019295:Computational Biology / Q000379:methods*; D030541:Databases, Genetic; D015964:Gene Expression Regulation, Bacterial; D016678:Genome; D016680:Genome, Bacterial; D006094:Gram-Positive Bacteria / Q000737:chemistry* / Q000378:metabolism; D006868:Hydrolysis; D020407:Internet; D008954:Models, Biological; D008969:Molecular Sequence Data; D005810:Multigene Family; D009113:Muramidase / Q000737:chemistry; D010457:Peptidoglycan / Q000737:chemistry*; D011134:Polysaccharides / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D013296:Streptococcus pneumoniae / Q000201:enzymology
D010457:Peptidoglycan; D011134:Polysaccharides; D011506:Proteins; D009113:Muramidase; D002794:Choline
J Biol Chem. 1999 Nov 5;274(45):32031-9
10542235
J Mol Biol. 2000 Jun 2;299(2):499-520
10860755
Anal Biochem. 2000 Sep 10;284(2):388-93
10964424
Nucleic Acids Res. 2001 Jan 1;29(1):126-7
11125068
J Mol Evol. 2001 Jan;52(1):78-84
11139297
Infect Immun. 2001 Mar;69(3):1593-8
11179332
Glycobiology. 2001 Mar;11(3):25R-36R
11320055
Science. 2001 Jul 20;293(5529):498-506
11463916
J Bacteriol. 2001 Oct;183(19):5709-17
11544234
Bioinformatics. 2001 Sep;17(9):845-6
11590103
Nat Struct Biol. 2001 Dec;8(12):1020-4
11694890
J Bacteriol. 2002 May;184(10):2595-602
11976287
Biochem Biophys Res Commun. 2002 Jul 26;295(4):952-7
12127987
J Bacteriol. 2002 Sep;184(18):4988-5000
12193614
J Bacteriol. 2002 Nov;184(22):6093-9
12399477
Microbiol Mol Biol Rev. 2002 Dec;66(4):702-38, table of contents
12456788
Nucleic Acids Res. 2003 Jan 1;31(1):383-7
12520028
Genome Biol. 2003;4(2):R11
12620121
Trends Biochem Sci. 2003 May;28(5):230-4
12765833
Trends Biochem Sci. 2003 May;28(5):234-7
12765834
Cell Mol Life Sci. 2003 Nov;60(11):2371-88
14625683
Nucleic Acids Res. 2004 Jan 1;32(Database issue):D138-41
14681378
Nucleic Acids Res. 2004;32(3):977-88
14960714
Infect Immun. 2004 Apr;72(4):1914-9
15039310
Mol Microbiol. 2004 Aug;53(4):1161-75
15306019
Eur J Biochem. 1987 May 4;164(3):621-4
3569279
Nature. 1994 Feb 24;367(6465):750-3
8107871
J Biol Chem. 1994 Aug 26;269(34):21603-7
8063800
Nucleic Acids Res. 1994 Nov 11;22(22):4673-80
7984417
Mol Microbiol. 1994 Aug;13(4):733-43
7997184
Curr Opin Struct Biol. 1994 Dec;4(6):810-3
7712284
Proteins. 1995 Jul;22(3):245-58
7479697
Protein Eng. 1997 Jan;10(1):1-6
9051728
Nucleic Acids Res. 1997 Sep 1;25(17):3389-402
9254694
Protein Eng. 1997 Jun;10(6):673-6
9278280
J Bacteriol. 1998 Feb;180(3):749-52
9457885
Microbiol Mol Biol Rev. 1998 Mar;62(1):181-203
9529891
Proc Natl Acad Sci U S A. 1998 May 26;95(11):5857-64
9600884
J Biol Chem. 1999 Mar 5;274(10):6726-34
10037771
Mol Microbiol. 1999 Jul;33(1):128-38
10411730