Crystal structure of Zika virus NS2B-NS3 protease in complex with a boronate inhibitor

被引：290

作者：

Lei, Jian ^{[1
,2
]}

Hansen, Guido ^{[1
]}

Nitsche, Christoph ^{[3
,4
]}

Klein, Christian D. ^{[3
]}

Zhang, Linlin ^{[1
,2
]}

Hilgenfeld, Rolf ^{[1
,2
]}

机构：

[1] Univ Lubeck, Inst Biochem, Ctr Struct & Cell Biol Med, Ratzeburger Allee 160, D-23562 Lubeck, Germany

[2] Univ Lubeck, German Ctr Infect Res DZIF, Hamburg Lubeck Borstel Riems Site, Lubeck, Germany

[3] Heidelberg Univ, Inst Pharm & Mol Biotechnol, Med Chem, Neuenheimer Feld 364, D-69120 Heidelberg, Germany

[4] Australian Natl Univ, Sch Chem, Canberra, ACT 2601, Australia

来源：

SCIENCE | 2016年 / 353卷 / 6298期

关键词：

NS3; PROTEASE; DENGUE;

D O I：

10.1126/science.aag2419

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The ongoing Zika virus (ZIKV) outbreak is linked to severe neurological disorders. ZIKV relies on its NS2B/NS3 protease for polyprotein processing; hence, this enzyme is an attractive drug target. The 2.7 angstrom crystal structure of ZIKV protease in complex with a peptidomimetic boronic acid inhibitor reveals a cyclic diester between the boronic acid and glycerol. The P2 4-aminomethylphenylalanine moiety of the inhibitor forms a salt-bridge with the nonconserved Asp(83) of NS2B; ion-pairing between Asp(83) and the P2 residue of the substrate likely accounts for the enzyme's high catalytic efficiency. The unusual dimer of the ZIKV protease: inhibitor complex seen in the crystal may provide a model for assemblies formed at high local concentrations of protease at the endoplasmatic reticulum membrane, the site of polyprotein processing.

引用

页码：503 / 505

页数：3

共 16 条

[1] DENV Inhibits Type I IFN Production in Infected Cells by Cleaving Human STING [J].

Aguirre, Sebastian ;

Maestre, Ana M. ;

Pagni, Sarah ;

Patel, Jenish R. ;

Savage, Timothy ;

Gutman, Delia ;

Maringer, Kevin ;

Bernal-Rubio, Dabeiba ;

Shabman, Reed S. ;

Simon, Viviana ;

Rodriguez-Madoz, Juan R. ;

Mulder, Lubbertus C. F. ;

Barber, Glen N. ;

Fernandez-Sesma, Ana .

PLOS PATHOGENS, 2012, 8 (10)

[2]

BEARCROFT W. G. C., 1956, TRANS ROY SOC TROP MED AND HYG, V50, P442, DOI 10.1016/0035-9203(56)90090-6

[3] Guillain-Barre Syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study [J].

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 .

LANCET, 2016, 387 (10027) :1531-1539

[4] Structural basis for the activation of flaviviral NS3 proteases from dengue and West Nile virus [J].

Erbel, P ;

Schiering, N ;

D'Arcy, A ;

Renatus, M ;

Kroemer, M ;

Lim, SP ;

Yin, Z ;

Keller, TH ;

Vasudevan, SG ;

Hommel, U .

NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2006, 13 (04) :372-373

[5] Zika virus in the Americas: Early epidemiological and genetic findings [J].

Faria, Nuno Rodrigues ;

da Silva Azevedo, Raimunda do Socorro ;

Kraemer, Moritz U. G. ;

Souza, Renato ;

Cunha, Mariana Sequetin ;

Hill, Sarah C. ;

Theze, Julien ;

Bonsall, Michael B. ;

Bowden, Thomas A. ;

Rissanen, Ilona ;

Rocco, Iray Maria ;

Nogueira, Juliana Silva ;

Maeda, Adriana Yurika ;

da Silva Vasami, Fernanda Giseli ;

de Lima Macedo, Fernando Luiz ;

Suzuki, Akemi ;

Rodrigues, Sueli Guerreiro ;

Ribeiro Cruz, Ana Cecilia ;

Nunes, Bruno Tardeli ;

de Almeida Medeiros, Daniele Barbosa ;

Guerreiro Rodrigues, Daniela Sueli ;

Nunes Queiroz, Alice Louize ;

Pinto da Silva, Eliana Vieira ;

Henriques, Daniele Freitas ;

Travassos da Rosa, Elisabeth Salbe ;

de Oliveira, Consuelo Silva ;

Martins, Livia Caricio ;

Vasconcelos, Helena Baldez ;

Neves Casseb, Livia Medeiros ;

Simith, Darlene de Brito ;

Messina, Jane P. ;

Abade, Leandro ;

Loureno, Jose ;

Junior Alcantara, Luiz Carlos ;

de Lima, Maricelia Maia ;

Giovanetti, Marta ;

Hay, Simon I. ;

de Oliveira, Rodrigo Santos ;

Lemos, Poliana da Silva ;

de Oliveira, Layanna Freitas ;

Silva de Lima, Clayton Pereira ;

da Silva, Sandro Patroca ;

de Vasconcelos, Janaina Mota ;

Franco, Luciano ;

Cardoso, Jedson Ferreira ;

da Silva Gonalves Vianez-Junior, Joao Lidio ;

Mir, Daiana ;

Bello, Gonzalo ;

Delatorre, Edson ;

Khan, Kamran .

SCIENCE, 2016, 352 (6283) :345-349

[6] Biology of Zika Virus Infection in Human Skin Cells [J].

Hamel, Rodolphe ;

Dejarnac, Ophelie ;

Wichit, Sineewanlaya ;

Ekchariyawat, Peeraya ;

Neyret, Aymeric ;

Luplertlop, Natthanej ;

Perera-Lecoin, Manuel ;

Surasombatpattana, Pornapat ;

Talignani, Loic ;

Thomas, Frederic ;

Cao-Lormeau, Van-Mai ;

Choumet, Valerie ;

Briant, Laurence ;

Despres, Philippe ;

Amara, Ali ;

Yssel, Hans ;

Misse, Dorothee .

JOURNAL OF VIROLOGY, 2015, 89 (17) :8880-8896

[7] Zika virus and microcephaly: why is this situation a PHEIC? [J].

Heymann, David L. ;

Hodgson, Abraham ;

Sall, Amadou Alpha ;

Freedman, David O. ;

Staples, J. Erin ;

Althabe, Fernando ;

Baruah, Kalpana ;

Mahmud, Ghazala ;

Kandun, Nyoman ;

Vasconcelos, Pedro F. C. ;

Bino, Silvia ;

Menon, K. U. .

LANCET, 2016, 387 (10020) :719-721

[8] Shape complementarity and hydrogen bond preferences in protein-protein interfaces: implications for antibody modeling and protein-protein docking [J].

Kuroda, Daisuke ;

Gray, Jeffrey J. .

BIOINFORMATICS, 2016, 32 (16) :2451-2456

[9] SHAPE COMPLEMENTARITY AT PROTEIN-PROTEIN INTERFACES [J].

LAWRENCE, MC ;

COLMAN, PM .

JOURNAL OF MOLECULAR BIOLOGY, 1993, 234 (04) :946-950

[10] Activity of recombinant dengue 2 virus NS3 protease in the presence of a truncated NS2B co-factor, small peptide substrates, and inhibitors [J].

Leung, D ;

Schroder, K ;

White, H ;

Fang, NX ;

Stoermer, MJ ;

Abbenante, G ;

Martin, JL ;

Young, PR ;

Fairlie, DP .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (49) :45762-45771

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