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Elucidation of a 2.3 Å Resolution Norovirus GII.4 Protease Structure by X‐Ray Crystallography
Author(s) -
Muzzarelli Kendall Marie,
Kuiper Benjamin,
Spellmon Nicholas,
Brunzelle Joseph,
Hackett Justin,
Kovari Iulia,
Yang Zhe,
Kovari Ladislau
Publication year - 2018
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.2018.32.1_supplement.526.47
Subject(s) - norovirus , protease , virology , computational biology , acute gastroenteritis , biology , enzyme , outbreak , biochemistry
According to a current report from the Centers for Disease Control (CDC), it is estimated that noroviruses are responsible for 685 million cases of acute gastroenteritis each year with an estimated $60 billion medically and socioeconomically. This overwhelming global burden drives the need for identification and characterization of potential norovirus drug targets to exploit for design and development. Specifically, the GII.4 norovirus genotype accounts for more than 50% of all outbreaks worldwide. Up until now, the only GII.4 model was based on an alignment of the GI.1 and GII.4 protease sequences which resulted in a sequence identity of only 67%. This high genetic diversity among human noroviruses enhances the need for an improved model of the GII.4 protease. We report the crystallization and structure elucidation of a 2.3Å resolution structure of the GII.4 norovirus protease (GII.4 NoV PR) through X‐ray crystallography. Additionally, extensive investigation and characterization of the GII.4 norovirus protease structure and mechanism were carried out through computational studies and enzyme kinetics. With the elucidation of the GII.4 norovirus protease structure, we hope to significantly improve the structure‐based design of both potent therapeutic inhibitors and potential vaccine strategies for future studies. Support or Funding Information Wayne State University School of Medicine This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .