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Conserved proline residues prevent dimerization and aggregation in the β‐lactamase BlaC

DOI: 10.1002/pro.4972 DOI Help

Authors: A. Chikunova (Leiden University) , M. P. Manley (Leiden University) , C. N. Heijjer (Leiden University) , C. S. Drenth (Leiden University) , A. J. Cramer-Blok (Leiden University) , M. Ud Din Ahmad (The Netherlands Cancer Institute) , A. Perrakis (The Netherlands Cancer Institute) , M. Ubbink (Leiden University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Protein Science , VOL 33

State: Published (Approved)
Published: April 2024
Diamond Proposal Number(s): 19800

Open Access Open Access

Abstract: Evolution leads to conservation of amino acid residues in protein families. Conserved proline residues are usually considered to ensure the correct folding and to stabilize the three-dimensional structure. Surprisingly, proline residues that are highly conserved in class A β-lactamases were found to tolerate various substitutions without large losses in enzyme activity. We investigated the roles of three conserved prolines at positions 107, 226, and 258 in the β-lactamase BlaC from Mycobacterium tuberculosis and found that mutations can lead to dimerization of the enzyme and an overall less stable protein that is prone to aggregate over time. For the variant Pro107Thr, the crystal structure shows dimer formation resembling domain swapping. It is concluded that the proline substitutions loosen the structure, enhancing multimerization. Even though the enzyme does not lose its properties without the conserved proline residues, the prolines ensure the long-term structural integrity of the enzyme.

Journal Keywords: beta-lactamase; conserved residues; dimerization; prolines

Diamond Keywords: Ezymes

Subject Areas: Biology and Bio-materials, Chemistry

Instruments: I04-1-Macromolecular Crystallography (fixed wavelength)

Other Facilities: X06SA at SLS

Added On: 29/03/2024 10:06

Discipline Tags:

Biochemistry Chemistry Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)