4dcb

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Y. pestis Plasminogen Activator Pla in Complex with Human Plasminogen Activation Loop Peptide ALP11Y. pestis Plasminogen Activator Pla in Complex with Human Plasminogen Activation Loop Peptide ALP11

Structural highlights

4dcb is a 2 chain structure with sequence from Homo sapiens and Yersinia pestis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.033Å
Ligands:, , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PLA_YERPE In the mammalian host activates (cleaves) plasminogen to generate the serine protease plasmin. Plasmin degrades fibrin clots (fibrinolysis) and facilitates bacterial cell migration, enabling rapid dissemination of bacteria from the initial site of infection (Probable). Cleaves host plasminogen to generate plasmin and probably also has autocatalytic activity (PubMed:20637417, PubMed:22645135). Fibrinolytic activity prevails at 37 degrees Celsius whereas coagulase expression predominates at lower temperatures (28 degrees Celsius) (PubMed:2526282). Cleaves plasminogen; plasminogen cleavage is much higher than coagulase activity (PubMed:20637417, PubMed:22645135, PubMed:2526282, PubMed:2651310).[1] [2] [3] [4] [5]

Publication Abstract from PubMed

Omptins constitute a unique family of outer membrane proteases that are widespread in Enterobacteriaceae. The plasminogen activator (Pla) of Yersinia pestis is an omptin family member that is very important for development of both bubonic and pneumonic plague. The physiological function of Pla is to cleave (activate) human plasminogen to form the plasma protease plasmin. Uniquely, lipopolysaccharide (LPS) is essential for the catalytic activity of all omptins, including Pla. Why omptins require LPS for enzymatic activity is unknown. Here, we report the co-crystal structure of LPS-free Pla in complex with the activation loop peptide of human plasminogen, its natural substrate. The structure shows that in the absence of LPS, the peptide substrate binds deep within the active site groove and displaces the nucleophilic water molecule, providing an explanation for the dependence of omptins on LPS for enzymatic activity.

Structural basis for activation of an integral membrane protease by lipopolysaccharide.,Eren E, van den Berg B J Biol Chem. 2012 Jul 6;287(28):23971-6. Epub 2012 May 29. PMID:22645135[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Eren E, Murphy M, Goguen J, van den Berg B. An active site water network in the plasminogen activator pla from Yersinia pestis. Structure. 2010 Jul 14;18(7):809-18. PMID:20637417 doi:10.1016/j.str.2010.03.013
  2. ↑ Eren E, van den Berg B. Structural basis for activation of an integral membrane protease by lipopolysaccharide. J Biol Chem. 2012 Jul 6;287(28):23971-6. Epub 2012 May 29. PMID:22645135 doi:10.1074/jbc.M112.376418
  3. ↑ McDonough KA, Falkow S. A Yersinia pestis-specific DNA fragment encodes temperature-dependent coagulase and fibrinolysin-associated phenotypes. Mol Microbiol. 1989 Jun;3(6):767-75. PMID:2526282 doi:10.1111/j.1365-2958.1989.tb00225.x
  4. ↑ Sodeinde OA, Goguen JD. Nucleotide sequence of the plasminogen activator gene of Yersinia pestis: relationship to ompT of Escherichia coli and gene E of Salmonella typhimurium. Infect Immun. 1989 May;57(5):1517-23. PMID:2651310 doi:10.1128/iai.57.5.1517-1523.1989
  5. ↑ Degen JL, Bugge TH, Goguen JD. Fibrin and fibrinolysis in infection and host defense. J Thromb Haemost. 2007 Jul;5 Suppl 1:24-31. PMID:17635705 doi:10.1111/j.1538-7836.2007.02519.x
  6. ↑ Eren E, van den Berg B. Structural basis for activation of an integral membrane protease by lipopolysaccharide. J Biol Chem. 2012 Jul 6;287(28):23971-6. Epub 2012 May 29. PMID:22645135 doi:10.1074/jbc.M112.376418

4dcb, resolution 2.03Å

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