Escherichia coli K-12 substr. MG1655 Enzyme: soluble lytic murein transglycosylase

Gene: slt Accession Numbers: EG10950 (EcoCyc), b4392, ECK4384

Synonyms: sltY, Slt70

Regulation Summary Diagram: ?

Regulation summary diagram for slt

Slt70 is involved in growth and recycling of peptidoglycan (PG) by catalyzing the lysis of the β-1,4 glycosidic bond between N-acetylmuramic acid and N-acetylglucosamine, producing 1,6-anhydromuropeptides at an optimal pH of 4.5 with a Km of 200 mg/L [Holtje75]. Slt70 may function as a PG quality control enzyme - the primary physiological function of Slt70 may be the degradation of uncrosslinked glycan strands thus preventing their aberrant incorporation into the PG matrix [Cho14].

Slt70 forms a murein-metabolizing multi-enzyme complex with PBP3 and PBP7/8 [Romeis94]. PBP7/8 was shown to stabilize and stimulate the activity of Slt70 [Romeis94]. Slt70 activity is also modulated by the stringent response [Betzner90].

The structure of Slt70 in it's native form and as a complex with 1,6-anhydromuropeptide has been determined by X-ray crystallography [Rozeboom90, Thunnissen94, Thunnissen95, vanAsselt99]; an N-terminal α-superhelical U domain plus a linker domain form a closed ring structure with a central hole which is capped by a C-terminal globular structure that contains the active site. The structure has also been determined as a complex with bulgecin A [Thunnissen95a], its inhibitor [Templin92].

Overproduction of Slt70 resulted in growth inhibition and lysis of some cells, but a deletion mutant had no observable phenotype [Engel91]. Mecillinam treatment of Δslt cells leads to a severely altered morphology due to the aberrant incorporation of peptidoglycan into the PG matrix; Slt70 is responsible for destroying the un-crosslinked glycan strands produced by β-lactam targeted PG synthetic enzymes [Cho14].

Constitutive activation of the Cpx two component pathway results in upregulation of slt (although no corresponding changes in peptidoglycan length could be observed); slt is a member of the CpxR regulon [BernalCabas14]

Review: [Holtje98]
Comment: [NunesAlves15]

Citations: [Kraft99, Heidrich02, Beachey81]

Locations: periplasmic space, membrane

Map Position: [4,628,756 -> 4,630,693] (99.76 centisomes, 359°)
Length: 1938 bp / 645 aa

Molecular Weight of Polypeptide: 73.353 kD (from nucleotide sequence), 65 kD (experimental) [Holtje75 ]

Unification Links: ASAP:ABE-0014404 , CGSC:34819 , EchoBASE:EB0943 , EcoGene:EG10950 , EcoliWiki:b4392 , ModBase:P0AGC3 , OU-Microarray:b4392 , PortEco:slt , PR:PRO_000023956 , Pride:P0AGC3 , Protein Model Portal:P0AGC3 , RefSeq:NP_418809 , RegulonDB:EG10950 , SMR:P0AGC3 , String:511145.b4392 , Swiss-Model:P0AGC3 , UniProt:P0AGC3

Relationship Links: CAZy:IN-FAMILY:GH23 , InterPro:IN-FAMILY:IPR000189 , InterPro:IN-FAMILY:IPR008258 , InterPro:IN-FAMILY:IPR008939 , InterPro:IN-FAMILY:IPR012289 , InterPro:IN-FAMILY:IPR016026 , InterPro:IN-FAMILY:IPR023346 , PDB:Structure:1QSA , PDB:Structure:1QTE , PDB:Structure:1SLY , Pfam:IN-FAMILY:PF01464 , Pfam:IN-FAMILY:PF14718 , Prosite:IN-FAMILY:PS00922

In Paralogous Gene Group: 67 (4 members) , 499 (2 members)

Gene-Reaction Schematic: ?

Gene-Reaction Schematic

Genetic Regulation Schematic: ?

Genetic regulation schematic for slt

GO Terms:

Biological Process: GO:0009253 - peptidoglycan catabolic process Inferred from experiment [Cho14]
GO:0000270 - peptidoglycan metabolic process Inferred by computational analysis [GOA01a]
GO:0071555 - cell wall organization Inferred by computational analysis [UniProtGOA11a]
Molecular Function: GO:0004553 - hydrolase activity, hydrolyzing O-glycosyl compounds Inferred from experiment Inferred by computational analysis [GOA01a, Engel91]
GO:0008933 - lytic transglycosylase activity Inferred by computational analysis Inferred from experiment [Engel91, GOA01a, Holtje75]
GO:0016829 - lyase activity Inferred by computational analysis [UniProtGOA11a]
GO:0016837 - carbon-oxygen lyase activity, acting on polysaccharides Inferred by computational analysis [GOA01]
Cellular Component: GO:0030288 - outer membrane-bounded periplasmic space Inferred from experiment Inferred by computational analysis [DiazMejia09, Han14, LopezCampistrou05, Walderich91, Engel91]
GO:0016020 - membrane Inferred by computational analysis [GOA01a]
GO:0042597 - periplasmic space Inferred by computational analysis [UniProtGOA11, UniProtGOA11a, GOA01a]

MultiFun Terms: cell processes cell division
cell structure murein
metabolism biosynthesis of macromolecules (cellular constituents) murein (peptidoglycan)

Essentiality data for slt knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB enriched Yes 37 Aerobic 6.95   Yes [Gerdes03, Comment 1]
LB Lennox Yes 37 Aerobic 7   Yes [Baba06, Comment 2]
M9 medium with 1% glycerol Yes 37 Aerobic 7.2 0.35 Yes [Joyce06, Comment 3]
MOPS medium with 0.4% glucose Yes 37 Aerobic 7.2 0.22 Yes [Baba06, Comment 2]
Yes [Feist07, Comment 4]

Last-Curated ? 17-Mar-2015 by Mackie A , Macquarie University

Enzymatic reaction of: murein hydrolase (soluble lytic murein transglycosylase)

Synonyms: lytic murein transglycosylase

EC Number: 4.2.2.-

a peptidoglycan dimer (generic)[periplasmic space] <=> a lipid II[periplasmic space] + GlcNAc-1,6-anhydro-MurNAc-pentapeptide[periplasmic space]

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

Reversibility of this reaction is unspecified.

Sequence Features

Protein sequence of soluble lytic murein transglycosylase with features indicated

Feature Class Location Common Name Citations Comment
Signal-Sequence 1 -> 27  
Protein-Structure-Region 28 -> 388 α superhelical U domain
Chain 28 -> 645  
UniProt: Soluble lytic murein transglycosylase;
Disulfide-Bond-Site 133, 166  
Amino-Acid-Sites-That-Bind 376, 378, 469, 475, 503, 617, 621, 624  
binding site for the peptide moieties of peptidoglycan
Protein-Structure-Region 405 -> 277 L domain
linker domain; connected to the superhelical U domain
Catalytic-Domain 478 -> 645 C-terminal domain
contains the active site; this domain forms a globular structure that packs on top of the ring structure formed by the U and L domains
Protein-Segment 492 -> 582  
UniProt: Slt-type domain; Sequence Annotation Type: region of interest;
Mutagenesis-Variant 505  
UniProt: Inactivates the enzyme.
Active-Site 505  
[UniProt15, vanAsselt99]
catalytic acid/base
Sequence-Conflict 583  
[Engel91, UniProt10]
UniProt: (in Ref. 1; AAA24634);

Gene Local Context (not to scale): ?

Gene local context diagram

Transcription Unit:

Transcription-unit diagram


Peter D. Karp on Wed Jan 18, 2006:
Gene left-end position adjusted based on analysis performed in the 2005 E. coli annotation update [Riley06 ].
10/20/97 Gene b4392 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10950; confirmed by SwissProt match.


Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554

Beachey81: Beachey EH, Keck W, de Pedro MA, Schwarz U (1981). "Exoenzymatic activity of transglycosylase isolated from Escherichia coli." Eur J Biochem 116(2);355-8. PMID: 7018908

BernalCabas14: Bernal-Cabas M, Ayala JA, Raivio T (2014). "The Cpx envelope stress response modifies peptidoglycan cross-linking via the L,D-transpeptidase LdtD and the novel protein YgaU." J Bacteriol. PMID: 25422305

Betzner90: Betzner AS, Ferreira LC, Holtje JV, Keck W (1990). "Control of the activity of the soluble lytic transglycosylase by the stringent response in Escherichia coli." FEMS Microbiol Lett 55(1-2);161-4. PMID: 1970319

Cho14: Cho H, Uehara T, Bernhardt TG (2014). "Beta-lactam antibiotics induce a lethal malfunctioning of the bacterial cell wall synthesis machinery." Cell 159(6);1300-11. PMID: 25480295

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

Engel91: Engel H, Kazemier B, Keck W (1991). "Murein-metabolizing enzymes from Escherichia coli: sequence analysis and controlled overexpression of the slt gene, which encodes the soluble lytic transglycosylase." J Bacteriol 173(21);6773-82. PMID: 1938883

Feist07: Feist AM, Henry CS, Reed JL, Krummenacker M, Joyce AR, Karp PD, Broadbelt LJ, Hatzimanikatis V, Palsson BO (2007). "A genome-scale metabolic reconstruction for Escherichia coli K-12 MG1655 that accounts for 1260 ORFs and thermodynamic information." Mol Syst Biol 3;121. PMID: 17593909

Gerdes03: Gerdes SY, Scholle MD, Campbell JW, Balazsi G, Ravasz E, Daugherty MD, Somera AL, Kyrpides NC, Anderson I, Gelfand MS, Bhattacharya A, Kapatral V, D'Souza M, Baev MV, Grechkin Y, Mseeh F, Fonstein MY, Overbeek R, Barabasi AL, Oltvai ZN, Osterman AL (2003). "Experimental determination and system level analysis of essential genes in Escherichia coli MG1655." J Bacteriol 185(19);5673-84. PMID: 13129938

GOA01: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

Han14: Han MJ, Kim JY, Kim JA (2014). "Comparison of the large-scale periplasmic proteomes of the Escherichia coli K-12 and B strains." J Biosci Bioeng 117(4);437-42. PMID: 24140104

Heidrich02: Heidrich C, Ursinus A, Berger J, Schwarz H, Holtje JV (2002). "Effects of multiple deletions of murein hydrolases on viability, septum cleavage, and sensitivity to large toxic molecules in Escherichia coli." J Bacteriol 184(22);6093-9. PMID: 12399477

Holtje75: Holtje JV, Mirelman D, Sharon N, Schwarz U (1975). "Novel type of murein transglycosylase in Escherichia coli." J Bacteriol 124(3);1067-76. PMID: 357

Holtje98: Holtje JV (1998). "Growth of the stress-bearing and shape-maintaining murein sacculus of Escherichia coli." Microbiol Mol Biol Rev 62(1);181-203. PMID: 9529891

Joyce06: Joyce AR, Reed JL, White A, Edwards R, Osterman A, Baba T, Mori H, Lesely SA, Palsson BO, Agarwalla S (2006). "Experimental and computational assessment of conditionally essential genes in Escherichia coli." J Bacteriol 188(23);8259-71. PMID: 17012394

Kraft99: Kraft AR, Prabhu J, Ursinus A, Holtje JV (1999). "Interference with murein turnover has no effect on growth but reduces beta-lactamase induction in Escherichia coli." J Bacteriol 181(23);7192-8. PMID: 10572120

LopezCampistrou05: Lopez-Campistrous A, Semchuk P, Burke L, Palmer-Stone T, Brokx SJ, Broderick G, Bottorff D, Bolch S, Weiner JH, Ellison MJ (2005). "Localization, annotation, and comparison of the Escherichia coli K-12 proteome under two states of growth." Mol Cell Proteomics 4(8);1205-9. PMID: 15911532

NunesAlves15: Nunes-Alves C (2015). "Antimicrobials: New tricks for old drugs." Nat Rev Microbiol 13(2);68. PMID: 25534806

Riley06: Riley M, Abe T, Arnaud MB, Berlyn MK, Blattner FR, Chaudhuri RR, Glasner JD, Horiuchi T, Keseler IM, Kosuge T, Mori H, Perna NT, Plunkett G, Rudd KE, Serres MH, Thomas GH, Thomson NR, Wishart D, Wanner BL (2006). "Escherichia coli K-12: a cooperatively developed annotation snapshot--2005." Nucleic Acids Res 34(1);1-9. PMID: 16397293

Romeis94: Romeis T, Holtje JV (1994). "Specific interaction of penicillin-binding proteins 3 and 7/8 with soluble lytic transglycosylase in Escherichia coli." J Biol Chem 269(34);21603-7. PMID: 8063800

Rozeboom90: Rozeboom HJ, Dijkstra BW, Engel H, Keck W (1990). "Crystallization of the soluble lytic transglycosylase from Escherichia coli K12." J Mol Biol 212(4);557-9. PMID: 2184239

Templin92: Templin MF, Edwards DH, Holtje JV (1992). "A murein hydrolase is the specific target of bulgecin in Escherichia coli." J Biol Chem 267(28);20039-43. PMID: 1400320

Thunnissen94: Thunnissen AM, Dijkstra AJ, Kalk KH, Rozeboom HJ, Engel H, Keck W, Dijkstra BW (1994). "Doughnut-shaped structure of a bacterial muramidase revealed by X-ray crystallography." Nature 367(6465);750-3. PMID: 8107871

Thunnissen95: Thunnissen AM, Isaacs NW, Dijkstra BW (1995). "The catalytic domain of a bacterial lytic transglycosylase defines a novel class of lysozymes." Proteins 22(3);245-58. PMID: 7479697

Thunnissen95a: Thunnissen AM, Rozeboom HJ, Kalk KH, Dijkstra BW (1995). "Structure of the 70-kDa soluble lytic transglycosylase complexed with bulgecin A. Implications for the enzymatic mechanism." Biochemistry 34(39);12729-37. PMID: 7548026

UniProt09: UniProt Consortium (2009). "UniProt version 15.8 released on 2009-10-01 00:00:00." Database.

UniProt10: UniProt Consortium (2010). "UniProt version 2010-11 released on 2010-11-02 00:00:00." Database.

UniProt10a: UniProt Consortium (2010). "UniProt version 2010-07 released on 2010-06-15 00:00:00." Database.

UniProt15: UniProt Consortium (2015). "UniProt version 2015-01 released on 2015-01-16 00:00:00." Database.

UniProtGOA11: UniProt-GOA (2011). "Gene Ontology annotation based on the manual assignment of UniProtKB Subcellular Location terms in UniProtKB/Swiss-Prot entries."

UniProtGOA11a: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."

vanAsselt99: van Asselt EJ, Thunnissen AM, Dijkstra BW (1999). "High resolution crystal structures of the Escherichia coli lytic transglycosylase Slt70 and its complex with a peptidoglycan fragment." J Mol Biol 291(4);877-98. PMID: 10452894

Walderich91: Walderich B, Holtje JV (1991). "Subcellular distribution of the soluble lytic transglycosylase in Escherichia coli." J Bacteriol 173(18);5668-76. PMID: 1885544

Other References Related to Gene Regulation

Huerta03: Huerta AM, Collado-Vides J (2003). "Sigma70 promoters in Escherichia coli: specific transcription in dense regions of overlapping promoter-like signals." J Mol Biol 333(2);261-78. PMID: 14529615

Raivio13: Raivio TL, Leblanc SK, Price NL (2013). "The Escherichia coli Cpx envelope stress response regulates genes of diverse function that impact antibiotic resistance and membrane integrity." J Bacteriol 195(12);2755-67. PMID: 23564175

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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
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