Substrate profiling of Zika virus NS2B-NS3 protease

被引:45
作者
Gruba, Natalia [1 ]
Martinez, Jose Ignacio Rodriguez [2 ]
Grzywa, Renata [3 ]
Wysocka, Magdalena [1 ]
Skorenski, Marcin [3 ]
Burmistrz, Michal [2 ,4 ]
Lecka, Maria [3 ]
Lesner, Adam [1 ]
Sienczyk, Marcin [3 ]
Pyrc, Krzysztof [2 ,4 ]
机构
[1] Univ Gdansk, Fac Chem, Dept Biochem, Wita Stwosza 63, PL-80952 Gdansk, Poland
[2] Jagiellonian Univ, Fac Biochem Biophys & Biotechnol, Dept Microbiol, Krakow, Poland
[3] Wroclaw Univ Sci & Technol, Fac Chem, Div Med Chem & Microbiol, Wybrzeze Wyspianskiego 27, PL-50370 Wroclaw, Poland
[4] Jagiellonian Univ, Malopolska Ctr Biotechnol, Krakow, Poland
来源
FEBS LETTERS | 2016年 / 590卷 / 20期
关键词
combinatorial chemistry; NS2B-NS3; protease; substrate library; substrate mapping; Zika virus; DENGUE VIRUS; NS3; PROTEASE; NS2B/NS3; SERINE-PROTEASE; LIGAND DOCKING; AMINO-ACIDS; DRUG DESIGN; SPECIFICITY; INHIBITORS; PROSPECTS;
D O I
10.1002/1873-3468.12443
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Zika virus (ZIKV), isolated from macaques in Uganda in 1947, was not considered to be a dangerous human pathogen. However, this view has recently changed as ZIKV infections are now associated with serious pathological disorders including microcephaly and Guillain-Barre syndrome. Similar to other viruses in the Flaviviridae family, ZIKV expresses the serine protease NS3 which is responsible for viral protein processing and replication. Herein, we report the expression of an active NS3(pro) domain fused with the NS2B cofactor (NS2B(LN)NS3(pro)) in a prokaryotic expression system and profile its specificity for synthesized FRET-type substrate libraries. Our findings pave way for screening potential intracellular substrates of NS3 and for developing specific inhibitors of this ZIKV protease.
引用
收藏
页码:3459 / 3468
页数:10
相关论文
共 42 条
  • [1] Structural evidence for regulation and specificity of flaviviral proteases and evolution of the Flaviviridae fold
    Aleshin, Alexander E.
    Shiryaev, Sergey A.
    Strongin, Alex Y.
    Liddington, Robert C.
    [J]. PROTEIN SCIENCE, 2007, 16 (05) : 795 - 806
  • [2] A P2 and P3 substrate specificity comparison between the Murray Valley encephalitis and West Nile virus NS2B/NS3 protease using C-terminal agmatine dipeptides
    Ang, Melgious Jin Yan
    Li, Zhitao
    Lim, Huichang Annie
    Ng, Fui Mee
    Then, Siew Wen
    Wee, John Liang Kuan
    Joy, Joma
    Hill, Jeffrey
    Chia, C. S. Brian
    [J]. PEPTIDES, 2014, 52 : 49 - 52
  • [3] Crystal Structure of a Novel Conformational State of the Flavivirus NS3 Protein: Implications for Polyprotein Processing and Viral Replication
    Assenberg, Rene
    Mastrangelo, Eloise
    Walter, Thomas S.
    Verma, Anil
    Milani, Mario
    Owens, Raymond J.
    Stuart, David I.
    Grimes, Jonathan M.
    Mancini, Erika J.
    [J]. JOURNAL OF VIROLOGY, 2009, 83 (24) : 12895 - 12906
  • [4] BEARCROFT W. G. C., 1956, TRANS ROY SOC TROP MED AND HYG, V50, P442, DOI 10.1016/0035-9203(56)90090-6
  • [5] The Medicinal Chemistry of Dengue Virus
    Behnam, Mira A. M.
    Nitsche, Christoph
    Boldescu, Veaceslav
    Klein, Christian D.
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2016, 59 (12) : 5622 - 5649
  • [6] Zika Virus Outbreak, Bahia, Brazil
    Campos, Gubio S.
    Bandeira, Antonio C.
    Sardi, Silvia I.
    [J]. EMERGING INFECTIOUS DISEASES, 2015, 21 (10) : 1885 - 1886
  • [7] Guillain-Barre Syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study
    Cao-Lormeau, Van-Mai
    Blake, Alexandre
    Mons, Sandrine
    Lastere, Stephane
    Roche, Claudine
    Vanhomwegen, Jessica
    Dub, Timothee
    Baudouin, Laure
    Teissier, Anita
    Larre, Philippe
    Vial, Anne-Laure
    Decam, Christophe
    Choumet, Valerie
    Halstead, Susan K.
    Willison, Hugh J.
    Musset, Lucile
    Manuguerra, Jean-Claude
    Despres, Philippe
    Fournier, Emmanuel
    Mallet, Henri-Pierre
    Musso, Didier
    Fontanet, Arnaud
    Neil, Jean
    Ghawche, Frederic
    [J]. LANCET, 2016, 387 (10027) : 1531 - 1539
  • [8] West Nile Virus NS2B/NS3 Protease As An Antiviral Target
    Chappell, K. J.
    Stoermer, M. J.
    Fairlie, D. P.
    Young, P. R.
    [J]. CURRENT MEDICINAL CHEMISTRY, 2008, 15 (27) : 2771 - 2784
  • [9] The Brazilian Zika virus strain causes birth defects in experimental models
    Cugola, Fernanda R.
    Fernandes, Isabella R.
    Russo, Fabiele B.
    Freitas, Beatriz C.
    Dias, Joao L. M.
    Guimaraes, Katia P.
    Benazzato, Cecilia
    Almeida, Nathalia
    Pignatari, Graciela C.
    Romero, Sarah
    Polonio, Carolina M.
    Cunha, Isabela
    Freitas, Carla L.
    Brandao, Wesley N.
    Rossato, Cristiano
    Andrade, David G.
    Faria, Daniele de P.
    Garcez, Alexandre T.
    Buchpigel, Carlos A.
    Braconi, Carla T.
    Mendes, Erica
    Sall, Amadou A.
    Zanotto, Paolo M. de A.
    Peron, Jean Pierre S.
    Muotri, Alysson R.
    Beltrao-Braga, Patricia C. B.
    [J]. NATURE, 2016, 534 (7606) : 267 - +
  • [10] ZIKA VIRUS .1. ISOLATIONS AND SEROLOGICAL SPECIFICITY
    DICK, GWA
    KITCHEN, SF
    HADDOW, AJ
    [J]. TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE, 1952, 46 (05) : 509 - 520