 |
PDBsum entry 3tx4
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Peptidoglycan binding protein
|
PDB id
|
|
|
|
3tx4
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
PDB id:
|
|
|
|
| Name: |
|
Peptidoglycan binding protein
|
|
|
Title:
|
|
Crystal structure of mutant (c354a) m. Tuberculosis ld-transpeptidase type 2
|
|
Structure:
|
|
Mycobacterium tuberculosis ld-transpeptidase type 2. Chain: a, b. Engineered: yes
|
|
Source:
|
|
Mycobacterium tuberculosis. Organism_taxid: 1773. Gene: lpps, mt2594, rv2518c. Expressed in: escherichia coli. Expression_system_taxid: 562.
|
|
Resolution:
|
|
|
2.32Å
|
R-factor:
|
0.213
|
R-free:
|
0.266
|
|
|
Authors:
|
|
S.Erdemli,M.A.Bianchet,R.Gupta,G.Lamichhane,L.M.Amzel
|
|
Key ref:
|
|
S.B.Erdemli
et al.
(2012).
Targeting the cell wall of Mycobacterium tuberculosis: structure and mechanism of L,D-transpeptidase 2.
Structure,
20,
2103-2115.
PubMed id:
|
|
|
Date:
|
|
|
22-Sep-11
|
Release date:
|
05-Dec-12
|
|
|
|
|
|
|
PROCHECK
|
|
|
|
|
|
Headers
|
|
|
|
References
|
|
|
|
|
|
|
|
O53223
(LDT2_MYCTO) -
L,D-transpeptidase 2 from Mycobacterium tuberculosis (strain CDC 1551 / Oshkosh)
|
|
|
|
Seq:
Struc:
|
|
|
|
408 a.a.
267 a.a.*
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Key: |
 |
PfamA domain |
|
|
 |
Secondary structure |
|
 |
CATH domain |
|
|
*
PDB and UniProt seqs differ
at 1 residue position (black
cross)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
|
Structure
20:2103-2115
(2012)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
Targeting the cell wall of Mycobacterium tuberculosis: structure and mechanism of L,D-transpeptidase 2.
|
|
S.B.Erdemli,
R.Gupta,
W.R.Bishai,
G.Lamichhane,
L.M.Amzel,
M.A.Bianchet.
|
|
|
|
|
| |
ABSTRACT
|
|
|
|
| |
|
|
With multidrug-resistant cases of tuberculosis increasing globally, better
antibiotic drugs and novel drug targets are becoming an urgent need. Traditional
β-lactam antibiotics that inhibit D,D-transpeptidases are not effective against
mycobacteria, in part because mycobacteria rely mostly on L,D-transpeptidases
for biosynthesis and maintenance of their peptidoglycan layer. This reliance
plays a major role in drug resistance and persistence of Mycobacterium
tuberculosis (Mtb) infections. The crystal structure at 1.7 Å resolution of
the Mtb L,D-transpeptidase Ldt(Mt2) containing a bound peptidoglycan fragment,
reported here, provides information about catalytic site organization as well as
substrate recognition by the enzyme. Based on our structural, kinetic, and
calorimetric data, we propose a catalytic mechanism for Ldt(Mt2) in which both
acyl-acceptor and acyl-donor substrates reach the catalytic site from the same,
rather than different, entrances. Together, this information provides vital
insights to facilitate development of drugs targeting this validated yet
unexploited enzyme.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
|
Links
