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| - | This is my practice page.
| + | ==Your Heading Here (maybe something like 'Structure')== |
| | + | <StructureSection load='5rsa' size='350' side='right' caption='' scene=''> |
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| - | <Structure load='4zjf' size='350' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' />
| + | Anything in this section will appear adjacent to the 3D structure and will be scrollable. |
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| - | | + | </StructureSection> |
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| - | <Structure load='Insert PDB code or filename here' size='350' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' /> | + | |
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| - | Cadmium uptake reduces the millimolar cellular accumulation of manganese and zinc, and thereby increases sensitivity to oxidative stress <ref>http://www.nature.com/articles/ncomms7418</ref>.
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| - | {|
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| - | | [[Image:details psaa avec mn.jpg]]
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| - | | [[Image:details psaa avec zn.jpg]]
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| - | | [[Image:ramachandran.png|400 px|right| thumb| Ramachandran blot of PsaA obtained by Lovell, Davis, ''et al.'' Proteins 50:437]]
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| - | == Function ==
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| - | Mn<sup>2+</sup> enables ''Streptococcus Pneunomiae'' to have a prompt and rapid growth. Superoxides are a key player in oxidative stress generated in the presence of iron. Therefore PsaA is essential for the existence of ''S. pneumoniae'' as mutations in the ''psaA'' gene cause deficiencies in growth but also in its virulence, adherence and the response to oxidative stress.
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| - | ===Adhesin and virulence===
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| - | PsaA is well hidden beneath the cell wall and the polysaccharide capsule, which is why it does not directly act as an adhesin as initially assumed. This was confirmed by studies on ''psaB'' and ''psaC'' deletion mutants which were not deficient in PsaA but showed impaired adherence, similar to ''psaA'' deletion mutants. As the disruption of either of the members of the Psa operon affects pneumococcal adherence, it seems that this process is coupled to the cellular Mn<sup>2+</sup> transport system. With bacterial adhesion being the first step in bacterial pathogenesis, the extinction of PsaA and the associated Psa operon lead to attenuated virulence in affected strains <ref name="ref3" />.
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| - | ===Virulence===
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| - | Next to its involvement in bacterial adhesion and the colonization in the human nasopharynx, ''S. pneumoniae'' actively produces H2O2 in large amounts to augment its own virulence on the one hand, and, on the other hand, to utilize it as a weapon in the competition against other pathogens <ref name="ref3" />. Mn<sup>2+</sup> is also required for the activity of CpsB, a tyrosine phosphatase involved in the regulation of capsule production. And in some streptococcal species, lectin-mediated adherence requires Mn<sup>2+</sup>. Finally, mutations in the psaBCA operon result in an almost complete attenuation of virulence for all tested models of animal infection.
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| - | ===Oxidative stress===
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| - | In ''S. pneumoniae'' H2O2 and superoxides are generated as toxic derivatives of molecular oxygen in several metabolic processes and during growth by [https://en.wikipedia.org/wiki/Pyruvate_oxidase ''pyruvate oxidase'']. Subsequently, H2O2 reacts with Fe<sup>2+</sup> during the [https://en.wikipedia.org/wiki/Fenton's_reagent ''Fenton reaction'']. This results in the formation of the hydroxylyl radical that causes severe damages in the cell. As a protective response against this oxidative stress, ''S. pneumoniae'' produces an [https://en.wikipedia.org/wiki/Superoxide_dismutase ''Mn<sup>2+</sup>-dependent superoxide dismutase''] (SodA) and the thiol peroxidase encoded by ''psaD'' in the Psa operon. Due to the use of H2O2 during pneumococcal virulence these two proteins and the dependence on Mn<sup>2+</sup> are of major importance. When Mn<sup>2+</sup> transport is disrupted, bacterial cells display hypersensitivity towards oxidative stress <ref name="ref3" />.
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| - | ==Interactions with other proteins==
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| - | - piaA, pneumococcal iron acquisition A which is an iron-compound ABC transporter permease. It is required for bacterial growth and full virulence in pulmonary infection.
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| - | -pavA, Pneumococcal adherence and virulence factor A is an adherence and virulence protein A. It binds fibronectin.
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| - | -Wzg, which regulates the capsule production and is an integral membrane regulatory protein Cps2A
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| - | -[https://www.wikigenes.org/e/gene/e/912478.html Tpx], a thiol peroxidase with a Has antioxidant activity. This protein can remove peroxides or H2O2 by similarity.
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| - | -[https://www.wikigenes.org/e/gene/e/933751.html PsaC], a manganese ABC transporter permease
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| - | -[https://www.wikigenes.org/e/gene/e/933772.html PsaB], a manganese ABC transporter ATP-binding protein. Deleting psaB results in decreased expression of PsaA. PsaC and psaC require Mn<sup>2+</sup> supplementation for growth and transformation.
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| - | -SPD_1450, an iron-dependent transcriptional regulator
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| - | -adcC, antibody-dependent cell-mediated cytotoxicity is a zinc ABC transporter ATP-binding protein.
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| - | -[https://www.wikigenes.org/e/gene/e/934852.html adcB], a zinc ABC transporter permease
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| - | == Disease ==
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| - | === Otitis media===
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| - | PsaA has been recognized to be involved in the adherence and virulence mechanisms of otitis media. ''Streptococcus pneumoniae'' is one of the main agents causing bacterial acute otitis media, directly or as complication of a viral upper respiratory tract infection. This disease is a highly prevalent pediatric disease worldwide. Hearing loss is a common problem associated with this disease. ''Streptococcus pneumoniae'' in middle ear can be resistant to penicillin and cephalosporin<ref>https://www.google.com/patents/US20130078254</ref>
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| - | === Pneumonia ===
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| - | PsaA protein is an indirect [https://en.wikipedia.org/wiki/Bacterial_adhesin adhesin] which is involved in colonization of the nasopharyngeal mucosal. Moreover, alveolar pneumonia is caused by the spread of ''Streptococcus pneumoniae'' from nasopharynx. Therefore PsaA protein is involved in infection of pulmonary parenchyma by ''Streptococcus pneumoniae''.
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| - | Sometimes, ''Streptococcus pneumoniae'' pass into the blood and causes a bacteremia besides pneumonia.
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| - | == Application in Biotechnology ==
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| - | PsaA is being actively evaluated as a component of a vaccin in formulations composed of pneumococcal common proteins. PsaA is a component of a vaccin because this protein is immunogenic and stimulates an increase in [https://en.wikipedia.org/wiki/Antibody antibody] production when the nasopharynx is naturally colonized. PsaA has been expressed as an ''E.coli'' recombinant protein, purified, and evaluated in a phase one clinical trial.
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| - | Progress in vaccine development is most advanced for ''Streptococcus pneumoniae''. Indeed, there is a seven-valent capsular-conjugate vaccine, [https://en.wikipedia.org/wiki/Pneumococcal_conjugate_vaccine PREVNAR®] but it is rather non efficient for otitis media.<ref>PMID:11176564</ref> PsaA has been shown to be an effective vaccine in animal models at preventing Streptococcus pneumoniae infection.
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| - | <math>Insert formula here</math>
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| - | ==References==
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| - | <references/>
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