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New insights into protein-DNA binding specificity from hydrogen bond based comparative study.

Maoxuan Lin | Jun-Tao Guo
Nucleic acids research | 2019

Knowledge of protein-DNA binding specificity has important implications in understanding DNA metabolism, transcriptional regulation and developing therapeutic drugs. Previous studies demonstrated hydrogen bonds between amino acid side chains and DNA bases play major roles in specific protein-DNA interactions. In this paper, we investigated the roles of individual DNA strands and protein secondary structure types in specific protein-DNA recognition based on side chain-base hydrogen bonds. By comparing the contribution of each DNA strand to the overall binding specificity between DNA-binding proteins with different degrees of binding specificity, we found that highly specific DNA-binding proteins show balanced hydrogen bonding with each of the two DNA strands while multi-specific DNA binding proteins are generally biased towards one strand. Protein-base pair hydrogen bonds, in which both bases of a base pair are involved in forming hydrogen bonds with amino acid side chains, are more prevalent in the highly specific protein-DNA complexes than those in the multi-specific group. Amino acids involved in side chain-base hydrogen bonds favor strand and coil secondary structure types in highly specific DNA-binding proteins while multi-specific DNA-binding proteins prefer helices.

Pubmed ID: 31665426

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Associated grants

  • Agency: NIGMS NIH HHS, United States
    Id: R15 GM110618

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CD-HIT (tool)

RRID:SCR_007105

THIS RESOURCE IS NO LONGER IN SERVICE. Documented on February 28,2023. Software program for clustering biological sequences with many applications in various fields such as making non-redundant databases, finding duplicates, identifying protein families, filtering sequence errors and improving sequence assembly etc. It is very fast and can handle extremely large databases. CD-HIT helps to significantly reduce the computational and manual efforts in many sequence analysis tasks and aids in understanding the data structure and correct the bias within a dataset. The CD-HIT package has CD-HIT, CD-HIT-2D, CD-HIT-EST, CD-HIT-EST-2D, CD-HIT-454, CD-HIT-PARA, PSI-CD-HIT, CD-HIT-OTU and over a dozen scripts. * CD-HIT (CD-HIT-EST) clusters similar proteins (DNAs) into clusters that meet a user-defined similarity threshold. * CD-HIT-2D (CD-HIT-EST-2D) compares 2 datasets and identifies the sequences in db2 that are similar to db1 above a threshold. * CD-HIT-454 identifies natural and artificial duplicates from pyrosequencing reads. * CD-HIT-OTU cluster rRNA tags into OTUs The usage of other programs and scripts can be found in CD-HIT user''s guide. CD-HIT was originally developed by Dr. Weizhong Li at Dr. Adam Godzik''s Lab at the Burnham Institute (now Sanford-Burnham Medical Research Institute).

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