Elizeu/sandbox/citocromo c

From Proteopedia

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User: Julie Langlois/Sandbox NCBI Accession: P42363.1 Uniprot Accesion: POA4G2 PDB ID: 3ZK7 Molecular weight: 34,538 kDa

Contents 1 Overview 1.1 PsaA protein 1.2 Streptococcus pneumoniae 2 Structure 3 Protein-protein interaction 4 Function 5 Disease 5.1 Meningitis 5.2 Otitis 5.3 Pneumonia 6 Application in Biotechnology

Overview

PsaA protein

PsaA (Pneumococcal surface antigen A) is a multi-functional lipoprotein detected on all known serotypes of Streptococcus pneumoniae. This lipoprotein belongs to the ABC-type transport protein complex that transports Mn2+. ABC means ATP binding complex. PsaA is also an adhesion factor that plays a major role in pneumococcal attachment to the host cell and virulence. PsaA is hidden beneath the cell wall. PsaA protein is involved in in colonization of the nasopharyngeal mucosal. This transporter is composed of the products of three genes, psaB (ATP-binding protein), psaC (integral membrane protein), and psaA (solute-binding lipoprotein), which are organized in an operon with a gene encoding PsaD, a thiol peroxidase.

Zinc in excess has significant toxicity to bacteria because it is an important innate defence mechanism. There are many Zinc in human body. Manganese is important for the virulence, growth and proliferation of Streptococcus pneumoniae. Zinc could compete for Manganese binding. However Manganese has more affinity for PsaA than Zinc but Zinc is not transported by the ABC-transporter. Zinc competition reduces intracellular Manganse resulting in up-regulation of PsaBCA expression.

Streptococcus pneumoniae

Streptococcus pneumoniae is a Gram positive cocci (with a diameter from 0.5 to 1 μm) and a member of the genus Streptococcus. It can live under aerobic or anaerobic conditions. It resides in the nasopharynx of healthy carriers. However the bacterium may become pathogenic in elderly and immunocompromised people and children. Then it can spread to other locations and cause disease. Its genome of S. pneumoniae is a closed, circular DNA structure that contains between 2.0 and 2.1 million base pairs.

Structure

spinqualitylabelsall models PDB ID 3ZK7 Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

This is 3D structure of PsaA in the metal-free, open state.

spinqualitylabelsall models PDB ID 3ZTT Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

This is 3D structure of PsaA with manganese.

This image shows the metal binding site in more detail, with the MntC residues and Manganese. Manganse ions are shown as purple spheres. We can see that Manganese interacts with Histine residues, Aspartique acid residues and Glutamique acid residues.

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Protein-protein interaction

Function

Disease

Meningitis

Otitis

Pneumonia

PsaA protein is an 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. Sometimes, Streptococcus pneumoniae pass into the blood and causes a bacteremia besides pneumonia.

Application in Biotechnology

PsaA is being actively evaluated as a component of a vaccin in formulations composed of pneumococcal common proteins. PsaA has been expressed as an E.coli recombinant protein, purified, and evaluated in a phase one clinical trial.