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Structural studies on Laz, a promiscuous anticancer Neisserial protein

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Title: Structural studies on Laz, a promiscuous anticancer Neisserial protein
Author(s): Chakrabarty, A.M.; Murata, K.; Hong, C.S.; Ochiai, A.; Hashimoto, W.
Subject(s): X-ray crystallography Neisseria Laz H.8 epitope Disorder Azurin
Abstract: Azurin and Laz (lipidated azurin) are 2 bacterial proteins with anticancer, anti-viral and anti-parasitic activities. Azurin, isolated from the bacterium Pseudomonas aeruginosa, termed Paz, demonstrates anticancer activity against a range of cancers but not against brain tumors. In contrast, Laz is produced by members of Gonococci/Meningococci, including Neisseria meningitides which can cross the blood-brain barrier to infect brain meninges. It has been previously reported that Laz has an additional 39 amino acid moiety, called an H.8 epitope, in the N-terminal part of the azurin moiety that allows Laz to cross the entry barrier to brain tumors such as glioblastomas. Exactly, how the H.8 epitope helps the azurin moiety of Laz to cross the entry barriers to attack glioblastoma cells is unknown. In this paper, we describe the structural features of the H.8 moiety in Laz using X-ray crystallography and demonstrate that while the azurin moiety of Laz adopts a β-sandwich fold with 2 β-sheets arranged in the Greek key motif, the H.8 epitope was present as a disordered structure outside the Greek key motif. Structures of Paz and H.8 epitope-deficient Laz are well superimposed. The structural flexibility of the H.8 motif in Laz explains the extracellular location of Laz in Neisseria where it can bind the key components of brain tumor cells to disrupt their tight junctions and allow entry of Laz inside the tumors to exert cytotoxicity.
Issue Date: 2015
Publisher: Taylor & Francis
Citation Info: Hashimoto, W., Ochiai, A., Hong, C. S., Murata, K., & Chakrabarty, A. M. (2015). Structural studies on Laz, a promiscuous anticancer Neisserial protein. Bioengineered, 6(3), 141-148. DOI: 10.1080/21655979.2015.1022303
Type: Article
Description: Post print version of article may differ from published version. This is an electronic version of an article published in Hashimoto, W., Ochiai, A., Hong, C. S., Murata, K., & Chakrabarty, A. M. (2015). Structural studies on Laz, a promiscuous anticancer Neisserial protein. Bioengineered, 6(3), 141-148. Bioengineered is available online at: http://www.informaworld.com/smpp/ DOI: 10.1080/21655979.2015.1022303
URI: http://hdl.handle.net/10027/20710
ISSN: 1949-1018
Date Available in INDIGO: 2016-06-08
 

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