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Structural and binding properties of the PASTA domain of PonA2, a key penicillin binding protein from Mycobacterium tuberculosis
Author(s) -
Calvanese Luisa,
Falcigno Lucia,
Maglione Cira,
Marasco Daniela,
Ruggiero Alessia,
Squeglia Flavia,
Berisio Rita,
D'Auria Gabriella
Publication year - 2014
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.22447
Subject(s) - chemistry , mycobacterium tuberculosis , penicillin , microbiology and biotechnology , penicillin binding proteins , tuberculosis , biochemistry , antibiotics , medicine , pathology , biology
PonA2 is one of the two class A penicillin binding proteins of Mycobacterium tuberculosis , the etiologic agent of tuberculosis. It plays a complex role in mycobacterial physiology and is spotted as a promising target for inhibitors. PonA2 is involved in adaptation of M. tuberculosis to dormancy, an ability which has been attributed to the presence in its sequence of a C‐terminal PASTA domain. Since PASTA modules are typically considered as β‐lactam antibiotic binding domains, we determined the solution structure of the PASTA domain from PonA2 and analyzed its binding properties versus a plethora of potential binders, including the β‐lactam antibiotics, two typical muropeptide mimics, and polymeric peptidoglycan. We show that, despite a high structural similarity with other PASTA domains, the PASTA domain of PonA2 displays different binding properties, as it is not able to bind muropeptides, or β‐lactams, or polymeric peptidoglycan. These results indicate that the role of PASTA domains cannot be generalized, as their specific binding properties strongly depend on surface residues, which are widely variable. © 2013 Wiley Periodicals, Inc. Biopolymers 101: 712–719, 2014.