PDBsum entry 4zfq

Transferase

PDB id: 4zfq

Contents

Protein chain

346 a.a.

Ligands

PEG ×2

DWZ

Waters ×43

PDB id:

4zfq

Name:

Transferase

Title:

Structure of m. Tuberculosis (3,3) l,d-transpeptidase, ldtmt5. (Meropenen-adduct form)

Structure:

L,d-transpeptidase 5. Chain: a. Synonym: ldt 5,ldt(mt5). Engineered: yes

Source:

Mycobacterium tuberculosis (strain cdc 1551 / oshkosh). Organism_taxid: 83331. Strain: cdc 1551 / oshkosh. Gene: mt0501. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.80Å R-factor: 0.232 R-free: 0.277

Authors:

L.Basta,A.Ghosh,G.Lamichhane,M.A.Bianchet

Key ref:

L.A.Brammer Basta et al. (2015). Loss of a Functionally and Structurally Distinct ld-Transpeptidase, LdtMt5, Compromises Cell Wall Integrity in Mycobacterium tuberculosis. J Biol Chem, 290, 25670-25685. PubMed id: 26304120 DOI: 10.1074/jbc.M115.660753

Date:

21-Apr-15 Release date: 02-Sep-15

Protein chain

P9WKV2  (LDT5_MYCTO) -  L,D-transpeptidase 5 from Mycobacterium tuberculosis (strain CDC 1551 / Oshkosh)

Seq: 451 a.a.

Struc: 346 a.a.

Enzyme reactions

• Enzyme class: E.C.2.3.2.- - ?????

DOI no: 10.1074/jbc.M115.660753

J Biol Chem 290:25670-25685 (2015)

PubMed id: 26304120

Loss of a Functionally and Structurally Distinct ld-Transpeptidase, LdtMt5, Compromises Cell Wall Integrity in Mycobacterium tuberculosis.

L.A.Brammer Basta, A.Ghosh, Y.Pan, J.Jakoncic, E.P.Lloyd, C.A.Townsend, G.Lamichhane, M.A.Bianchet.

ABSTRACT

The final step of peptidoglycan (PG) biosynthesis in bacteria involves cross-linking of peptide side chains. This step in Mycobacterium tuberculosis is catalyzed by ld- and dd-transpeptidases that generate 3→3 and 4→3 transpeptide linkages, respectively. M. tuberculosis PG is predominantly 3→3 cross-linked, and LdtMt2 is the dominant ld-transpeptidase. There are four additional sequence paralogs of LdtMt2 encoded by the genome of this pathogen, and the reason for this apparent redundancy is unknown. Here, we studied one of the paralogs, LdtMt5, and found it to be structurally and functionally distinct. The structures of apo-LdtMt5 and its meropenem adduct presented here demonstrate that, despite overall architectural similarity to LdtMt2, the LdtMt5 active site has marked differences. The presence of a structurally divergent catalytic site and a proline-rich C-terminal subdomain suggest that this protein may have a distinct role in PG metabolism, perhaps involving other cell wall-anchored proteins. Furthermore, M. tuberculosis lacking a functional copy of LdtMt5 displayed aberrant growth and was more susceptible to killing by crystal violet, osmotic shock, and select carbapenem antibiotics. Therefore, we conclude that LdtMt5 is not a functionally redundant ld-transpeptidase, but rather it serves a unique and important role in maintaining the integrity of the M. tuberculosis cell wall.