Files and links (2)
Published, Version of Record (VoR)CC BY V4.0, Open
Journal article
Structures of full-length VanR from Streptomyces coelicolor in both the inactive and activated states
Acta crystallographica. Section D, Structural biology, v 77(8), pp 1027-1039
01 Aug 2021
PMID: 34342276
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Vancomycin has historically been used as a last-resort treatment for serious bacterial infections. However, vancomycin resistance has become widespread in certain pathogens, presenting a serious threat to public health. Resistance to vancomycin is conferred by a suite of resistance genes, the expression of which is controlled by the VanR-VanS two-component system. VanR is the response regulator in this system; in the presence of vancomycin, VanR accepts a phosphoryl group from VanS, thereby activating VanR as a transcription factor and inducing expression of the resistance genes. This paper presents the X-ray crystal structures of full-length VanR from Streptomyces coelicolor in both the inactive and activated states at resolutions of 2.3 and 2.0 angstrom, respectively. Comparison of the two structures illustrates that phosphorylation of VanR is accompanied by a disorder-to-order transition of helix 4, which lies within the receiver domain of the protein. This transition generates an interface that promotes dimerization of the receiver domain; dimerization in solution was verified using analytical ultracentrifugation. The inactive conformation of the protein does not appear intrinsically unable to bind DNA; rather, it is proposed that in the activated form DNA binding is enhanced by an avidity effect contributed by the receiver-domain dimerization.
Metrics
Details
- Title
- Structures of full-length VanR from Streptomyces coelicolor in both the inactive and activated states
- Creators
- Lina J. Maciunas - Drexel UniversityNadia Porter - Drexel UniversityPaula J. Lee - Drexel UniversityKushol Gupta - University of PennsylvaniaPatrick J. Loll - Drexel University
- Publication Details
- Acta crystallographica. Section D, Structural biology, v 77(8), pp 1027-1039
- Publisher
- Int Union Crystallography
- Number of pages
- 13
- Grant note
- P30 GM124165 / National Institute of General Medical Sciences from the National Institutes of Health; General Electric DE-SC0012704; DE-AC02-06CH11357 / DOE Office of Science; United States Department of Energy (DOE) S10OD018483 / NIH High-End Instrumentation Grant; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA S10OD021527 / NIH-ORIP HEI grant DE-SC0012704 / DOE Office of Biological and Environmental Research; United States Department of Energy (DOE) P30GM133893 / National Institutes of Health, National Institute of General Medical Sciences (NIGMS); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:000681698200006
- Scopus ID
- 2-s2.0-85112065774
- Other Identifier
- 991019170451304721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemical Research Methods
- Biochemistry & Molecular Biology
- Biophysics
- Crystallography