title: Structural and binding properties of the PASTA domain of PonA2, a key penicillin binding protein from Mycobacterium tuberculosis.
abstract: 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.
authors.affiliation: CIRPeB, University of Naples Federico II, Naples, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Calvanese
authors.forename: Lucia
authors.initials: L
authors.lastname: Falcigno
authors.forename: Cira
authors.initials: C
authors.lastname: Maglione
authors.forename: Daniela
authors.initials: D
authors.lastname: Marasco
authors.forename: Alessia
authors.initials: A
authors.lastname: Ruggiero
authors.forename: Flavia
authors.initials: F
authors.lastname: Squeglia
authors.forename: Rita
authors.initials: R
authors.lastname: Berisio
authors.forename: Gabriella
authors.initials: G
authors.lastname: D'Auria
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D002151:Calorimetry / Q000379:methods; D002942:Circular Dichroism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D009169:Mycobacterium tuberculosis / Q000378:metabolism*; D046915:Penicillin-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D010457:Peptidoglycan / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D058767:Protein Unfolding; D013696:Temperature; D047090:beta-Lactams / Q000737:chemistry / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D046915:Penicillin-Binding Proteins; D010457:Peptidoglycan; D047090:beta-Lactams
keywords: binding; structure; tuberculosis