Structural studies on Laz, a promiscuous anticancer Neisserial protein
| Autor: | Chang Soo Hong, Wataru Hashimoto, Akihito Ochiai, Ananda M. Chakrabarty, Kousaku Murata |
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| Rok vydání: | 2015 |
| Předmět: |
Meningitides
Protein Conformation Molecular Sequence Data Antineoplastic Agents Bioengineering Applied Microbiology and Biotechnology Epitope Tight Junctions Protein structure Bacterial Proteins X-Ray Diffraction Azurin Cell Line Tumor Escherichia coli Humans Moiety Amino Acid Sequence Peptide sequence chemistry.chemical_classification biology Brain General Medicine biology.organism_classification Amino acid chemistry Biochemistry Pseudomonas aeruginosa Neisseria Research Paper Biotechnology |
| Zdroj: | Bioengineered. 6:141-148 |
| ISSN: | 2165-5987 2165-5979 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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