UniProt functional annotation for O53223



	UniProt functional annotation for O53223

UniProt code: O53223.

Organism: Mycobacterium tuberculosis (strain CDC 1551 / Oshkosh).

Taxonomy: Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae; Mycobacterium; Mycobacterium tuberculosis complex.

Function: Generates 3->3 cross-links in peptidoglycan, catalyzing the cleavage of the mDap(3)-D-Ala(4) bond of a tetrapeptide donor stem and the formation of a bond between the carbonyl of mDap(3) of the donor stem and the side chain of mDap(3) of the acceptor stem. Is specific for donor substrates containing a stem tetrapeptide since it cannot use pentapeptide stems. Is essential for virulence in a mouse model of acute infection. {ECO:0000269|PubMed:20305661}.

Activity regulation: Is irreversibly inactivated by the beta-lactams carbapenems via the formation of a covalent adduct resulting from acylation of the catalytic Cys. {ECO:0000250}.

Pathway: Cell wall biogenesis; peptidoglycan biosynthesis.

Subunit: Monomer. {ECO:0000305|PubMed:23103390}.

Subcellular location: Cell membrane {ECO:0000255|PROSITE- ProRule:PRU00303}; Lipid-anchor {ECO:0000255|PROSITE-ProRule:PRU00303}.

Induction: Is expressed at a level higher than other LDT paralogs at all phases of growth. {ECO:0000269|PubMed:20305661}.

Disruption phenotype: Inactivation of this gene leads to altered colony morphology and growth, attenuation of persistence and increased susceptibility to amoxicillin-clavulanate both in vitro and in the mouse model during the chronic phase of infection. Loss of both ldtMt1 and ldtMt2 results in phenotypes that are unique and/or severe compared to the single mutants lacking only ldtMt1 or ldtMt2. The double gene deletion severely alters cellular shape, intracellular morphology, physiology and virulence: the length of mutant cells are shorter than wild-type, they have deep surface depressions and bulges, they possess large unstained vacuole-like structures, the thickness of the peptidoglycan layer is smaller, the protein localization is altered, and in vitro and in vivo growth and virulence are severely attenuated. Moreover, double-mutant cells are more sensitive to vancomycin and amoxicillin-clavulanate. {ECO:0000269|PubMed:20305661, ECO:0000269|PubMed:24464457}.

Annotations taken from UniProtKB at the EBI.


Organism:		Mycobacterium tuberculosis (strain CDC 1551 / Oshkosh).
Taxonomy:		Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae; Mycobacterium; Mycobacterium tuberculosis complex.



Function:		Generates 3->3 cross-links in peptidoglycan, catalyzing the cleavage of the mDap(3)-D-Ala(4) bond of a tetrapeptide donor stem and the formation of a bond between the carbonyl of mDap(3) of the donor stem and the side chain of mDap(3) of the acceptor stem. Is specific for donor substrates containing a stem tetrapeptide since it cannot use pentapeptide stems. Is essential for virulence in a mouse model of acute infection. {ECO:0000269\|PubMed:20305661}.


Activity regulation:		Is irreversibly inactivated by the beta-lactams carbapenems via the formation of a covalent adduct resulting from acylation of the catalytic Cys. {ECO:0000250}.
Pathway:		Cell wall biogenesis; peptidoglycan biosynthesis.
Subunit:		Monomer. {ECO:0000305\|PubMed:23103390}.
Subcellular location:		Cell membrane {ECO:0000255\|PROSITE- ProRule:PRU00303}; Lipid-anchor {ECO:0000255\|PROSITE-ProRule:PRU00303}.
Induction:		Is expressed at a level higher than other LDT paralogs at all phases of growth. {ECO:0000269\|PubMed:20305661}.
Disruption phenotype:		Inactivation of this gene leads to altered colony morphology and growth, attenuation of persistence and increased susceptibility to amoxicillin-clavulanate both in vitro and in the mouse model during the chronic phase of infection. Loss of both ldtMt1 and ldtMt2 results in phenotypes that are unique and/or severe compared to the single mutants lacking only ldtMt1 or ldtMt2. The double gene deletion severely alters cellular shape, intracellular morphology, physiology and virulence: the length of mutant cells are shorter than wild-type, they have deep surface depressions and bulges, they possess large unstained vacuole-like structures, the thickness of the peptidoglycan layer is smaller, the protein localization is altered, and in vitro and in vivo growth and virulence are severely attenuated. Moreover, double-mutant cells are more sensitive to vancomycin and amoxicillin-clavulanate. {ECO:0000269\|PubMed:20305661, ECO:0000269\|PubMed:24464457}.