Identification of recurring protein structure microenvironments and discovery of novel functional sites around CYS residues.

BMC Structural Biology
Shirley WuRuss B Altman

Abstract

The emergence of structural genomics presents significant challenges in the annotation of biologically uncharacterized proteins. Unfortunately, our ability to analyze these proteins is restricted by the limited catalog of known molecular functions and their associated 3D motifs. In order to identify novel 3D motifs that may be associated with molecular functions, we employ an unsupervised, two-phase clustering approach that combines k-means and hierarchical clustering with knowledge-informed cluster selection and annotation methods. We applied the approach to approximately 20,000 cysteine-based protein microenvironments (3D regions 7.5 A in radius) and identified 70 interesting clusters, some of which represent known motifs (e.g. metal binding and phosphatase activity), and some of which are novel, including several zinc binding sites. Detailed annotation results are available online for all 70 clusters at http://feature.stanford.edu/clustering/cys. The use of microenvironments instead of backbone geometric criteria enables flexible exploration of protein function space, and detection of recurring motifs that are discontinuous in sequence and diverse in structure. Clustering microenvironments may thus help to functionally chara...Continue Reading

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Citations

May 11, 2011·BMC Proceedings·Trafina S JadhavMichael C Wooten
Jun 7, 2018·Frontiers in Genetics·Nadia RaboanatahiryMaoteng Li
May 15, 2020·Journal of the American Chemical Society·Karine MazmanianCarmay Lim

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Software Mentioned

BLEST
Clust1
Sub25
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PocketPicker
Sub48
Clust4
FEATURE
lxml

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