Počet záznamů: 1
Allostery, Recognition of Nascent Peptidoglycan, and Cross-linking of the Cell Wall by the Essential Penicillin-Binding Protein 2x of Streptococcus pneumoniae
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SYSNO ASEP 0488994 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Allostery, Recognition of Nascent Peptidoglycan, and Cross-linking of the Cell Wall by the Essential Penicillin-Binding Protein 2x of Streptococcus pneumoniae Tvůrce(i) Bernardo-Garcia, N. (ES)
Mahasenan, K.V. (US)
Batuecas, M.T. (ES)
Lee, M. (US)
Hesek, D. (US)
Petráčková, Denisa (MBU-M) RID, ORCID
Doubravová, Linda (MBU-M) ORCID, RID
Branny, Pavel (MBU-M) RID, ORCID
Mobashery, S. (US)
Hermoso, J. A. (ES)Zdroj.dok. ACS Chemical Biology. - : American Chemical Society - ISSN 1554-8929
Roč. 13, č. 3 (2018), s. 694-702Poč.str. 9 s. Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova RESISTANT STAPHYLOCOCCUS-AUREUS ; BETA-LACTAM-BINDING ; KINASE STKP Vědní obor RIV CE - Biochemie Obor OECD Biochemistry and molecular biology CEP GAP207/12/1568 GA ČR - Grantová agentura ČR Institucionální podpora MBU-M - RVO:61388971 UT WOS 000428003000027 EID SCOPUS 85044017924 DOI 10.1021/acschembio.7b00817 Anotace Transpeptidases, members of the penicillin-binding protein (PBP) families, catalyze cross-linking of the bacterial cell wall. This transformation is critical for the survival of bacteria, and it is the target of inhibition by beta-lactam antibiotics. We report herein our structural insights into catalysis by the essential PBP2x of Streptococcus pneumoniae by disclosing a total of four X-ray structures, two computational models based on the crystal structures, and molecular dynamics simulations. The X-ray structures are for the apo PBP2x, the enzyme modified covalently in the active site by oxacillin (a penicillin antibiotic), the enzyme modified by oxacillin in the presence of a synthetic tetrasaccharide surrogate for the cell-wall peptidoglycan, and a noncovalent complex of cefepime (a cephalosporin antibiotic) bound to the active site. A prerequisite for catalysis by transpeptidases, including PBP2x, is the molecular recognition of nascent peptidoglycan strands, which harbor pentapeptide stems. We disclose that the recognition of nascent peptidoglycan by PBP2x takes place by complexation of one pentapeptide stem at an allosteric site located in the PASTA domains of this enzyme. This binding predisposes the third pentapeptide stem in the same nascent peptidoglycan strand to penetration into the active site for the turnover events. The complexation of the two pentapeptide stems in the same peptidoglycan strand is a recognition motif for the nascent peptidoglycan, critical for the cell-wall cross-linking reaction. Pracoviště Mikrobiologický ústav Kontakt Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231 Rok sběru 2019
Počet záznamů: 1