Escherichia coli K-12 substr. MG1655 Enzyme: membrane-bound lytic murein transglycosylase A

Gene: mltA Accession Numbers: G7457 (EcoCyc), b2813, ECK2809

Synonyms: ygdM, mlt, Mlt38

Regulation Summary Diagram: ?

Regulation summary diagram for mltA

MltA is one of six (along with MltB, MltC, MltD, EmtA, and Slt70) major lytic endotransglycosylases expressed in Escherichia coli. MltA is responsible for cleaving β-1,4 glycosidic bonds between the N-acetylglucosamine and N-acetylmuramic acid residues of peptidoglycan polymers and for catalyzing the intramolecular transglycosylation of the muramic acid residue resulting in 1,6-anhydro-muropeptides.

MltA and MltB are expressed as membrane-bound lipoproteins. Sucrose gradient centrifugation studies have shown that MltA is localized to the outer membrane [Lommatzsch97]. Overexpression of MltA resulted in elevated levels of a membrane fraction protein with a molecular mass corresponding to the mass of the purified MltA protein [Ursinus94]. Expression of MltA in cells grown in the presence of H-3 palmitate followed by SDS-PAGE analysis resulted in fluorographic visualization of a labeled band corresponding to the 39 kDa mass of MltA, demonstrating the lipoprotein character of MltA [Hussain80]. MltA was shown to bind specifically to MipA which binds PBP1B, forming a trimeric complex [Vollmer99]. MltA co-purifies with PBP1B, PBP1C, PBP2, PBP3, PBP1A through an unknown periplasmic factor, and MipA [Vollmer99].

The structure of MltA has been determined by X-ray crystallography at resolutions of 2.00 Å [vanStraaten05], and 2.50 Å [Powell06]. The structures of two forms of a MltA mutant (apo-1 and apo-2) and of the MltA mutant in complex with a substrate analog have been determined at resolutions of 2.46 Å, 2.25 Å, and 2.25 Å, respectively [vanStraaten07].

Induced overexpression of MltA resulted in lysis of cells grown at 30 degrees Celsius, the optimal temperature for enzymatic activity, but not at 37 degrees [Lommatzsch97]. Furthermore the expressed activity was able to hydrolyze both murein sacculi as well as isolated glycan strands [Lommatzsch97, Ursinus94]. MltA is able to hydrolyze murein sacculi with a Km of 52.6 mg/liter and a Vmax of 2.2 mg/liter/min [Ursinus94]. A triple mltA, mltB, and slt70 mutant resulted in a 72% reduction in murein turnover [Kraft99].

Reviews: [Holtje98, Vollmer01]

Citations: [Barends05, Van04a, Engel92a]

Locations: cytosol, inner membrane, outer membrane

Map Position: [2,944,103 <- 2,945,200] (63.45 centisomes, 228°)
Length: 1098 bp / 365 aa

Molecular Weight of Polypeptide: 40.411 kD (from nucleotide sequence), 39 kD (experimental) [Hussain80 ]

Unification Links: ASAP:ABE-0009228 , DIP:DIP-51238N , EchoBASE:EB2894 , EcoGene:EG13085 , EcoliWiki:b2813 , OU-Microarray:b2813 , PortEco:mltA , PR:PRO_000023245 , Pride:P0A935 , Protein Model Portal:P0A935 , RefSeq:NP_417293 , RegulonDB:G7457 , SMR:P0A935 , String:511145.b2813 , UniProt:P0A935

Relationship Links: CAZy:IN-FAMILY:GH102 , InterPro:IN-FAMILY:IPR005300 , InterPro:IN-FAMILY:IPR009009 , InterPro:IN-FAMILY:IPR010611 , InterPro:IN-FAMILY:IPR014733 , InterPro:IN-FAMILY:IPR026044 , PDB:Structure:2AE0 , PDB:Structure:2GAE , PDB:Structure:2pi8 , PDB:Structure:2pic , PDB:Structure:2pjj , Pfam:IN-FAMILY:PF03562 , Pfam:IN-FAMILY:PF06725 , Prosite:IN-FAMILY:PS51257 , Smart:IN-FAMILY:SM00925

Gene-Reaction Schematic: ?

Gene-Reaction Schematic

GO Terms:

Biological Process: GO:0000910 - cytokinesis Inferred from experiment [Heidrich02]
GO:0009252 - peptidoglycan biosynthetic process Inferred from experiment [Ursinus94]
GO:0009254 - peptidoglycan turnover 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, Ursinus94]
GO:0008933 - lytic transglycosylase activity Inferred from experiment [Ursinus94]
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:0005829 - cytosol Inferred from experiment [Ishihama08]
GO:0005887 - integral component of plasma membrane Inferred from experiment [Ursinus94]
GO:0016021 - integral component of membrane Inferred from experiment [Ursinus94]
GO:0009279 - cell outer membrane Inferred by computational analysis [UniProtGOA11, UniProtGOA11a, Lommatzsch97]
GO:0016020 - membrane Inferred by computational analysis [UniProtGOA11a]
GO:0019867 - outer membrane Inferred by computational analysis [GOA01a]

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

Essentiality data for mltA 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 ? 22-Oct-2007 by Johnson A , JCVI

Enzymatic reaction of: murein hydrolase (membrane-bound lytic murein transglycosylase A)

Synonyms: lytic murein transglycosylase

EC Number: 4.2.2.-

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

pH(opt): 4.5 [Ursinus94]

Sequence Features

Protein sequence of membrane-bound lytic murein transglycosylase A with features indicated

Feature Class Location Common Name Citations Comment
Signal-Sequence 1 -> 20  
Chain 21 -> 365  
UniProt: Membrane-bound lytic murein transglycosylase A;
Lipid-Binding-Site 21 MltA aminoacylation site
Sequence-Conflict 346  
[Lommatzsch97, UniProt10a]
UniProt: (in Ref. 1; AAC45723);

Gene Local Context (not to scale): ?

Gene local context diagram

Transcription Unit:

Transcription-unit diagram


3/2/1998 (pkarp) Merged genes G330/b2813 and G7457/mltA
Markus Krummenacker on Tue Oct 14, 1997:
Gene object created from Blattner lab Genbank (v. M52) entry.


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

Barends05: Barends TR, de Jong RM, van Straaten KE, Thunnissen AM, Dijkstra BW (2005). "Escherichia coli MltA: MAD phasing and refinement of a tetartohedrally twinned protein crystal structure." Acta Crystallogr D Biol Crystallogr 61(Pt 5);613-21. PMID: 15858272

Engel92a: Engel H, Smink AJ, van Wijngaarden L, Keck W (1992). "Murein-metabolizing enzymes from Escherichia coli: existence of a second lytic transglycosylase." J Bacteriol 174(20);6394-403. PMID: 1356966

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."

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

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

Hussain80: Hussain M, Ichihara S, Mizushima S (1980). "Accumulation of glyceride-containing precursor of the outer membrane lipoprotein in the cytoplasmic membrane of Escherichia coli treated with globomycin." J Biol Chem 255(8);3707-12. PMID: 6988430

Ishihama08: Ishihama Y, Schmidt T, Rappsilber J, Mann M, Hartl FU, Kerner MJ, Frishman D (2008). "Protein abundance profiling of the Escherichia coli cytosol." BMC Genomics 9;102. PMID: 18304323

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

Lommatzsch97: Lommatzsch J, Templin MF, Kraft AR, Vollmer W, Holtje JV (1997). "Outer membrane localization of murein hydrolases: MltA, a third lipoprotein lytic transglycosylase in Escherichia coli." J Bacteriol 179(17);5465-70. PMID: 9287002

Powell06: Powell AJ, Liu ZJ, Nicholas RA, Davies C (2006). "Crystal structures of the lytic transglycosylase MltA from N.gonorrhoeae and E.coli: insights into interdomain movements and substrate binding." J Mol Biol 359(1);122-36. PMID: 16618494

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

UniProt10a: UniProt Consortium (2010). "UniProt version 2010-11 released on 2010-11-02 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."

Ursinus94: Ursinus A, Holtje JV (1994). "Purification and properties of a membrane-bound lytic transglycosylase from Escherichia coli." J Bacteriol 176(2);338-43. PMID: 8288527

Van04a: Van Straaten KE, Dijkstra BW, Thunnissen AM (2004). "Purification, crystallization and preliminary X-ray analysis of the lytic transglycosylase MltA from Escherichia coli." Acta Crystallogr D Biol Crystallogr 60(Pt 4);758-60. PMID: 15039577

vanStraaten05: van Straaten KE, Dijkstra BW, Vollmer W, Thunnissen AM (2005). "Crystal structure of MltA from Escherichia coli reveals a unique lytic transglycosylase fold." J Mol Biol 352(5);1068-80. PMID: 16139297

vanStraaten07: van Straaten KE, Barends TR, Dijkstra BW, Thunnissen AM (2007). "Structure of Escherichia coli Lytic transglycosylase MltA with bound chitohexaose: implications for peptidoglycan binding and cleavage." J Biol Chem 282(29);21197-205. PMID: 17502382

Vollmer01: Vollmer W, Holtje JV (2001). "Morphogenesis of Escherichia coli." Curr Opin Microbiol 4(6);625-33. PMID: 11731312

Vollmer99: Vollmer W, von Rechenberg M, Holtje JV (1999). "Demonstration of molecular interactions between the murein polymerase PBP1B, the lytic transglycosylase MltA, and the scaffolding protein MipA of Escherichia coli." J Biol Chem 274(10);6726-34. PMID: 10037771

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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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