Biology:Plasminogen activator Pla

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Plasminogen activator Pla
Identifiers
EC number3.4.23.48
CAS number101028-08-4
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum

Plasminogen activator Pla (EC 3.4.23.48) is an enzyme.[1] This enzyme catalyses the following chemical reaction

Converts human Glu-plasminogen to plasmin by cleaving the Arg560-Val peptide bond that is also hydrolysed by the mammalian u-plasminogen activator and t-plasminogen activator. Also cleaves arginyl bonds in other proteins.

This enzyme is isolated from the bacterium Yersinia pestis that causes plague. Y. pestis carries a 9.5-kb plasmid, pPCP1, that encodes the plasminogen activator.[2] Pla is a critical virulence factor for plague. In bubonic plague, Pla promotes the invasion of Y. pestis from subcutaneous sites of inoculation into the lymphatic system and deeper tissues.[2] In contrast, Pla is important for bacterial growth in the lung during pneumonic plague but it is not required for dissemination to other tissues.[3] It is found in the outer membrane of gram-negative bacteria, and it functions as a surface protease and an adhesin. It has suggested that the fate of Y.pestis infection of the lung is decided extremely early during infection, and that Pla plays a dual role to tilt the balance in favor of the pathogen.[3] In the initial stages of infection, Pla inhibits the activation of complement system and neutrophil-mediated killing such as phagocytosis and degranulation with its proteolytic activity. In addition, with its adhesin function, it suppresses the neutrophil influx, and facilitates type three secretion system (T3SS) to deliver multiple toxic Yersinia effector proteins Yops directly into target cells to inhibit the cytokine signalling.[3]

References

  1. "Protein regions important for plasminogen activation and inactivation of alpha2-antiplasmin in the surface protease Pla of Yersinia pestis". Molecular Microbiology 40 (5): 1097–1111. June 2001. doi:10.1046/j.1365-2958.2001.02451.x. PMID 11401715. 
  2. 2.0 2.1 "A plasminogen-activating protease specifically controls the development of primary pneumonic plague". Science 315 (5811): 509–513. January 2007. doi:10.1126/science.1137195. PMID 17255510. 
  3. 3.0 3.1 3.2 "A Dual Role for the Plasminogen Activator Protease During the Preinflammatory Phase of Primary Pneumonic Plague". The Journal of Infectious Diseases 222 (3): 407–416. July 2020. doi:10.1093/infdis/jiaa094. PMID 32128567. 

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