Detailed microscopic study of the full ZipA : FtsZ interface

• Type: Article in International Scientific Journal
• Date: 2006

Authors

Moreira, IS (Author) Other; Fernandes, PA (Author) FCUP; Ramos, MJ (Author) FCUP

Journal

Title: Proteins: Structure, Function and Genetics

Vol. 63

Pages: 811-821

ISSN: 0887-3585

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 20 Citations

Scopus - 20 Citations

Scientific classification

FOS: Natural sciences > Biological sciences

Other information

Authenticus ID: P-004-KM8

DOI: 10.1002/prot.20944

Abstract (EN): Protein-protein interaction networks are very important for a wide range of biological processes. Crystallographic structures and mutational studies have generated a large number of information that allowed the discovery of energetically important determinants of specificity at intermolecular protein interfaces and the understanding of the structural and energetic characteristics of the binding hot spots. In this study we have used the improved MMPB/SA (molecular mechanics/Poisson-Boltzmann surface area) approach that combining molecular mechanics and continuum solvent permits to calculate the free energy differences upon alanine mutation. For a better understanding of the binding determinants of the complex formed between the FtsZ fragment and ZipA we extended the alanine scanning mutagenesis study to all interfacial residues of this complex. As a result, we present new mutations that allowed the discovery of residues for which the binding free energy differences upon alanine mutation are higher than 2.0 kcal/mol. We also observed the formation of a hydrophobic pocket with a high warm spot spatial complementarity between FtsZ and ZipA. Small molecules could be designed to bind to these amino acid residues hindering the binding of FtsZ to ZipA. Hence, these mutational data can be used to design new drugs to control more efficiently bacterial infections.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11