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Ultra High‐throughput Screening Uncovers New Activities in Phosphatases of the Haloalkanoic Acid Dehalogenase Superfamily (HADSF)
Author(s) -
Farelli Jeremiah D,
Huang Hua,
Liu Chunliang,
Pandya Chetanya,
Al Obaidi Nawar F,
Hillerich Brandan S.,
Love James D,
Almo Steven C,
DunawayMariano Debra,
Allen Karen N
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.571.1
Subject(s) - computational biology , biology , druggability , genome , dephosphorylation , dehalogenase , protein function , annotation , function (biology) , drug discovery , protein sequencing , genetics , gene , peptide sequence , phosphatase , bioinformatics , phosphorylation
Since the first genomes were sequenced, there has been an exponential increase of protein sequences deposited into databases worldwide. This increase in sequence data has allowed for dramatic improvements in our understanding of the metabolism of organisms. Unfortunately, as the number of protein sequences grows, the number of definitive functional assignments diminishes. Current methods involve comparison of sequence identity between known proteins and newly sequenced ones. As the sequence identity decreases, proteins are annotated as “hypothetical,” and certainty in annotation shrinks. Thus a strategy for reliably determining protein function is necessary. The HADSF consists of Mg 2+ ‐dependent enzymes that catalyze a wide range of reactions including dehalogenation, phosphoryltransfer and dephosphorylation. Here we present the role that high‐throughput screening (HTS) might play in functional discovery for families with members having common chemical function but divergence in physiological substrate (e.g., kinases). We highlight five areas of discovery enabled by the HTS‐guided substrate profiling: 1) uncovering new metabolic pathways, 2) tracking of orthologs, 3) distribution of promiscuous versus specific family members, 4) annotation of hypothetical proteins, 5) functional assignment of proteins with known structures. This research is supported by the NIGMS (U54 GM093342).