Albany 2019: 20th Conversation - Abstracts

category image Albany 2019
Conversation 20
June 11-15 2019
Adenine Press (2019)

Annotation of cysteine functions in unknown proteins – a new approach based on protein microenvironments

Huge disparity exists in terms of number of sequenced proteins, experimentally available protein structures and functionally characterized proteins. With the advent of proteomic techniques large number of structures are solved for “proteins of unknown functions” (PUFs). More than 20% of the known protein domains are characterized as “domains of unknown function” (DUFs). Bacteria and eukaryotes share near about 1000 DUFs. Evolutionary conservation suggests that DUFs are essential in both eukaryotes and bacterial pathogens. However, the function of those proteins and involvement of important amino acids in protein functions remain elusive. Characterization of functions even for a few proteins or domains is experimentally laborious and time consuming. Here we present annotation of cysteine amino acid functions based on protein microenvironments in known protein dataset and apply those annotations to unknown proteins. Protein microenvironment is described by two parameters, buried fraction (BF) and rHpy (a quantitative property descriptor to describe the hydrophobicity of local environment around an amino acid) (Bandyopadhyay and Mehler 2008). Cysteine functions were curated from literature and structures were obtained PDB database with resolution greater than 1.5Å. Statistically meaningful characterization was done for four cysteine modifications, namely, disulphide formation (Bhatnagar et.al. 2016), thioether formation, sulfenylation and metal binding (Bhatnagar and Bandyopadhyay 2018). Distinct contours (within the space of BF and rHpy) were identified for different cysteine modifications. Training sets on four cysteine functions were validated on test sets of cysteines obtained from protein structures in PDB database with resolution lower than 1.5 Å. These contours will be exploited to annotate cysteine functions in PUFs and DUFs.


    Bandyopadhyay, D. and Mehler, E.L., “Quantitative Expression of Protein Heterogeneity: Response of Amino Acid Side Chains to Their Local Environment”, Proteins: Structure, Function and Bioinformatics, 2008; 72, 646-59

    Bhatnagar, A., Apostol, M. I., Bandyopadhyay, D., "Amino acid function relates to its embedded protein microenvironment: A study on disulphide-bridged cystine", Proteins: Structure Function Bioinformatics 2016 84, 1576-1589

    Bhatnagar, A. and Bandyopadhyay, D., “Characterization of cysteine thiol modifications based on protein microenvironments and local secondary structures”, Proteins; Structure, Function and Bioinformatics 2018, 86, 192-209

Debashree Bandyopadhyay
Akshay Bhatnagar
Shubham Paliwal


Birla Institute of Technology and Science
Pilani, Hyderabad Campus
Hyderabad, 500078, India

E-mail: banerjee.debi@hyderabad.bits-pilani.ac.in