UniProt functional annotation for O53638



	UniProt functional annotation for O53638

UniProt code: O53638.

Organism: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).

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 thought to play a role in adaptation to the nonreplicative state of M.tuberculosis. {ECO:0000269|PubMed:18408028, ECO:0000269|PubMed:24041897}.

Activity regulation: Is irreversibly inactivated by the beta-lactams carbapenems via the formation of a covalent adduct resulting from acylation of the catalytic Cys; ertapenem and imipenem are the most efficient drugs for in vitro LdtMt1 inactivation. Cephalosporins (cefotaxime, cephalothin, and ceftriaxone) also form covalent adducts with LdtMt1, although the acylation reaction was 7- to 1,000-fold slower and leads to elimination of one of the drug side chains. A high drug concentration (360 uM) of ceftriaxone is required for full inhibition of enzyme activity. Is not inhibited by ampicillin. {ECO:0000269|PubMed:18408028, ECO:0000269|PubMed:22615283, ECO:0000269|PubMed:24041897}.

Pathway: Cell wall biogenesis; peptidoglycan biosynthesis.

Subunit: Monomer. {ECO:0000269|PubMed:23999293}.

Subcellular location: Periplasm {ECO:0000305}.

Induction: Up-regulated 17-fold under nutrient starvation. {ECO:0000269|PubMed:11929527}.

Domain: Consists of two domains connected by a short loop, which form a bent shape. The N-terminal domain (residues 32-122) resembles a c-type immunoglobulin (Ig) domain, and the C-terminal contains the catalytic site that is located in a tiny tunnel. {ECO:0000269|PubMed:23999293}.

Miscellaneous: The peptidoglycan structure of stationary-phase M.tuberculosis is atypical since it contains a majority (80%) of 3->3 cross-links synthesized by L,D-transpeptidases that predominate over the 4->3 cross-links formed by the D,D-transpeptidase activity of classical penicillin-binding proteins (PubMed:18408028). In fact, 3-3 cross-linkages predominate throughout all growth phases and the ratio of 4-3/3-3 linkages does not vary significantly under any growth condition (PubMed:22906310). {ECO:0000305|PubMed:18408028}.

Annotations taken from UniProtKB at the EBI.


Organism:		Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
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 thought to play a role in adaptation to the nonreplicative state of M.tuberculosis. {ECO:0000269\|PubMed:18408028, ECO:0000269\|PubMed:24041897}.


Activity regulation:		Is irreversibly inactivated by the beta-lactams carbapenems via the formation of a covalent adduct resulting from acylation of the catalytic Cys; ertapenem and imipenem are the most efficient drugs for in vitro LdtMt1 inactivation. Cephalosporins (cefotaxime, cephalothin, and ceftriaxone) also form covalent adducts with LdtMt1, although the acylation reaction was 7- to 1,000-fold slower and leads to elimination of one of the drug side chains. A high drug concentration (360 uM) of ceftriaxone is required for full inhibition of enzyme activity. Is not inhibited by ampicillin. {ECO:0000269\|PubMed:18408028, ECO:0000269\|PubMed:22615283, ECO:0000269\|PubMed:24041897}.
Pathway:		Cell wall biogenesis; peptidoglycan biosynthesis.
Subunit:		Monomer. {ECO:0000269\|PubMed:23999293}.
Subcellular location:		Periplasm {ECO:0000305}.
Induction:		Up-regulated 17-fold under nutrient starvation. {ECO:0000269\|PubMed:11929527}.
Domain:		Consists of two domains connected by a short loop, which form a bent shape. The N-terminal domain (residues 32-122) resembles a c-type immunoglobulin (Ig) domain, and the C-terminal contains the catalytic site that is located in a tiny tunnel. {ECO:0000269\|PubMed:23999293}.
Miscellaneous:		The peptidoglycan structure of stationary-phase M.tuberculosis is atypical since it contains a majority (80%) of 3->3 cross-links synthesized by L,D-transpeptidases that predominate over the 4->3 cross-links formed by the D,D-transpeptidase activity of classical penicillin-binding proteins (PubMed:18408028). In fact, 3-3 cross-linkages predominate throughout all growth phases and the ratio of 4-3/3-3 linkages does not vary significantly under any growth condition (PubMed:22906310). {ECO:0000305\|PubMed:18408028}.