Flexibility in a Drug Transport Accessory Protein: Molecular Dynamics Simulations of MexA
| Autor: | Vaccaro, L, Koronakis, V, Sansom, MS, Sansom, M |
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| Rok vydání: | 2006 |
| Předmět: |
Models
Molecular Biophysics Biophysical Theory and Modeling Protein Structure Secondary 03 medical and health sciences Molecular dynamics Protein structure Drug Resistance Bacterial Inner membrane Computer Simulation 030304 developmental biology 0303 health sciences Principal Component Analysis biology Membrane transport protein 030302 biochemistry & molecular biology Signal transducing adaptor protein Membrane Transport Proteins Periplasmic space Protein Structure Tertiary Biochemistry biology.protein Bacterial outer membrane Function (biology) Bacterial Outer Membrane Proteins |
| Zdroj: | Biophysical Journal. 91(2):558-564 |
| ISSN: | 0006-3495 |
| DOI: | 10.1529/biophysj.105.080010 |
| Popis: | Drug resistance in Gram-negative bacteria may be conferred via efflux through a tripartite complex of an inner membrane pump, an outer membrane pore, and a periplasmic adaptor protein. These are AcrB, TolC, and AcrA, respectively, in Escherichia coli. In Pseudomonas aerugonisa, their homologs are MexB, OprM, and MexA. Defining the interdomain dynamics of the adaptor protein is essential to understanding the mechanism of complex formation. Extended (25ns) molecular dynamics simulations of MexA have been performed to determine such interdomain dynamics. Analysis of conformational drift demonstrates substantial motions of the three domains of MexA relative to one another. Principal components analysis reveals a hinge-bending motion and rotation of the α-helical hairpin relative to the other domains to be the two dominant motions. These two motions provide an element of considerable flexibility which is likely to be exploited in the adaptor function of MexA. |
| Databáze: | OpenAIRE |
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