Your browser doesn't support javascript.
loading
Protein structural ensembles are revealed by redefining X-ray electron density noise.
Lang, P Therese; Holton, James M; Fraser, James S; Alber, Tom.
Affiliation
  • Lang PT; Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720.
Proc Natl Acad Sci U S A ; 111(1): 237-42, 2014 Jan 07.
Article in En | MEDLINE | ID: mdl-24363322
To increase the power of X-ray crystallography to determine not only the structures but also the motions of biomolecules, we developed methods to address two classic crystallographic problems: putting electron density maps on the absolute scale of e(-)/Å(3) and calculating the noise at every point in the map. We find that noise varies with position and is often six to eight times lower than thresholds currently used in model building. Analyzing the rescaled electron density maps from 485 representative proteins revealed unmodeled conformations above the estimated noise for 45% of side chains and a previously hidden, low-occupancy inhibitor of HIV capsid protein. Comparing the electron density maps in the free and nucleotide-bound structures of three human protein kinases suggested that substrate binding perturbs distinct intrinsic allosteric networks that link the active site to surfaces that recognize regulatory proteins. These results illustrate general approaches to identify and analyze alternative conformations, low-occupancy small molecules, solvent distributions, communication pathways, and protein motions.
Subject(s)
Key words

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Protein Kinases / Proteins / Crystallography, X-Ray / Electrons Type of study: Prognostic_studies Limits: Humans Language: En Journal: Proc Natl Acad Sci U S A Year: 2014 Type: Article

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Protein Kinases / Proteins / Crystallography, X-Ray / Electrons Type of study: Prognostic_studies Limits: Humans Language: En Journal: Proc Natl Acad Sci U S A Year: 2014 Type: Article