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Folding of class A beta-lactamases is rate-limited by peptide bond isomerization and occurs via parallel pathways

Title data

Vandenameele, Julie ; Lejeune, Annabelle ; di Paolo, Alexandre ; Brans, Alain ; Frère, Jean-Marie ; Schmid, Franz X. ; Matagne, André:
Folding of class A beta-lactamases is rate-limited by peptide bond isomerization and occurs via parallel pathways.
In: Biochemistry. Vol. 49 (18 May 2010) Issue 19 . - pp. 4264-4275.
ISSN 1520-4995
DOI: https://doi.org/10.1021/bi100369d

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Abstract in another language

Class A beta-lactamases (M(r) approximately 29000) provide good models for studying the folding mechanism of large monomeric proteins. In particular, the highly conserved cis peptide bond between residues 166 and 167 at the active site of these enzymes controls important steps in their refolding reaction. In this work, we analyzed how conformational folding, reactivation, and cis/trans peptide bond isomerizations are interrelated in the folding kinetics of beta-lactamases that differ in the nature of the cis peptide bond, which involves a Pro167 in the BS3 and TEM-1 enzyme, a Leu167 in the NMCA enzyme, and which is missing in the PER-1 enzyme. The analysis of folding by spectroscopic probes and by the regain of enzymatic activity in combination with double-mixing procedures indicates that conformational folding can proceed when the 166-167 bond is still in the incorrect trans form. The very slow trans --> cis isomerization of the Glu166-Xaa167 peptide bond, however, controls the final step of folding and is required for the regain of the enzymatic activity. This very slow phase is absent in the refolding of PER-1, in which the Glu166-Ala167 peptide bond is trans. The double-mixing experiments revealed that a second slow kinetic phase is caused by the cis/trans isomerization of prolines that are trans in the folded proteins. The folding of beta-lactamases is best described by a model that involves parallel pathways. It highlights the role of peptide bond cis/trans isomerization as a kinetic determinant of folding.

Further data

Item Type: Article in a journal
Refereed: Yes
Additional notes: PubMed-ID: 20384356
Institutions of the University: Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Former Professors > Professorship Biochemistry - Univ.-Prof. Dr. Franz Xaver Schmid
Faculties
Faculties > Faculty of Biology, Chemistry and Earth Sciences
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Professorship Biochemistry
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Former Professors
Result of work at the UBT: Yes
DDC Subjects: 500 Science > 540 Chemistry
Date Deposited: 22 Apr 2015 09:02
Last Modified: 10 Jun 2015 09:37
URI: https://eref.uni-bayreuth.de/id/eprint/10556