Abstract：
:In this chapter, we first briefly review the history of Zika virus (ZIKV) over the past 70 years since its discovery. We then focus on the ZIKV NS2B/NS3 protease, a major potential target for anti-ZIKV therapeutics. We describe the structure of the complex between Zika virus NS2B-NS3 protease and a peptide boronic-acid inhibitor that we determined in early 2016. We then review other structural studies on the Zika virus protease, which have been published in the past few months. Three different types of construct for the protease have been investigated by X-ray crystallography and NMR spectroscopy: the traditional "linked" construct comprising the NS2B cofactor, a Gly4SerGly4 linker, and the NS3pro chain; a construct where the linker has been replaced by Lys-Thr-Gly-Lys-Arg, which leads to autocleavage; and the bimolecular "unlinked" protease consisting of the NS2B cofactor segment and NS3pro. In complex with an inhibitor, the protease adopts a closed, "active" conformation with the NS2B chain wrapped around the NS3pro and contributing to the S2 pocket. In the ligand-free state, the Gly4SerGly4-linked enzyme adopts an open or relaxed conformation, with the C-terminal half of the NS2B cofactor highly flexible and disordered. Very surprisingly, however, the "unlinked", bimolecular protease has been reported to adopt the closed conformation in the crystal, even though, apparently, no peptide was bound to the substrate-binding site. The Gly4SerGly4-linked enzyme has been used successfully in drug discovery efforts.
journal_name
Adv Exp Med Bioljournal_title
Advances in experimental medicine and biologyauthors
Hilgenfeld R,Lei J,Zhang Ldoi
10.1007/978-981-10-8727-1_10subject
Has Abstractpub_date
2018-01-01 00:00:00pages
131-145eissn
0065-2598issn
2214-8019journal_volume
1062pub_type
杂志文章,评审abstract：:The presence and significance of tumor hypoxia has been recognized since the 1950's. Hypoxic cells in vitro and in animal tumors in vivo are documented to be three times more resistant to radiation-induced killing compared to aerobic cells. There is now evidence that tumor hypoxia is treatment-limiting in many human c...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
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journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
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journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
doi：10.1007/978-1-4684-3273-2_20
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journal_title：Advances in experimental medicine and biology
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abstract：:Pioneered by the classical mouse embryonic stem cells (ESCs), various stem cell lines representing the peri- and postimplantation stages of embryogenesis have been established. To gain insight into the gene regulatory network operating in these cells, we first investigated epiblast stem cells (EpiSCs), performing ChIP...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
doi：10.1007/978-981-10-7311-3_17
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journal_title：Advances in experimental medicine and biology
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doi：10.1007/978-1-4757-0259-0_21
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journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
doi：10.1007/978-1-4939-2981-8_53
更新日期：2016-01-01 00:00:00
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journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
doi：10.1007/978-1-4615-3426-6_28
更新日期：1992-01-01 00:00:00
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journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
doi：10.1007/978-3-030-36214-0_9
更新日期：2020-01-01 00:00:00
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journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
doi：10.1007/978-94-007-4549-0_19
更新日期：2013-01-01 00:00:00
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doi：10.1007/978-3-030-13845-5_5
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journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
doi：10.1007/978-94-007-7893-1_14
更新日期：2014-01-01 00:00:00
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journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
doi：10.1007/978-981-10-3233-2_14
更新日期：2017-01-01 00:00:00
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journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
doi：10.1007/978-0-387-34133-0_28
更新日期：2006-01-01 00:00:00
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journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
doi：10.1007/978-1-4684-5826-8_2
更新日期：1990-01-01 00:00:00
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pub_type： 杂志文章
doi：10.1007/978-1-4419-9029-7_51
更新日期：2003-01-01 00:00:00
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journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
doi：10.1007/978-3-319-09614-8_23
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journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
doi：10.1007/978-1-4615-1885-3_31
更新日期：1995-01-01 00:00:00
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journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
doi：
更新日期：2008-01-01 00:00:00
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journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
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更新日期：2018-01-01 00:00:00
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journal_title：Advances in experimental medicine and biology
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pub_type： 杂志文章,评审
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更新日期：2014-01-01 00:00:00
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pub_type： 杂志文章
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更新日期：1996-01-01 00:00:00
abstract：:Mouse embryonic stem cells (mESCs) release into the medium in which they are cultured heterogeneous populations of microvesicles (mESMVs), important components of cell-cell communication, that transfer their contents not only to other stem cells but also to cells of other origins. The purpose of these studies was to d...
journal_title：Advances in experimental medicine and biology
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更新日期：2016-01-01 00:00:00
abstract：:The experimental use of capsaicin has made possible the discovery that chemosensitive neurons participate in the activation of endogenous mechanisms of protection in the face of pending injury to the gastric mucosa. At present, the pathophysiological potential of this neural emergency system is best reflected by the g...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
doi：
更新日期：1995-01-01 00:00:00
