Subtilisin

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Subtilisin
Image:1st2.png
Crystal structure of Subtilisin
Gene code:
Structure:
Recent publications:

Subtilisin (serine endopeptidase) is a proteolytic enzyme initially obtained from Bacillus subtilis. It is secreted in large amounts from many Bacillus species.

The structure of subtilisin has been determined by X-ray crystallography. It is a 275 residue globular protein with several alpha-helices, and a large beta-sheet. It is structurally unrelated to the chymotrypsin-clan of serine proteases, but uses the same type of catalytic triad in the active site. This makes it the classic example of convergent evolution.

Charge-relay Site of Subtilisin

The active site features a charge-relay network involving Asp-32, His-64, and active site Ser-221 arranged in a catalytic triad. The charge-relay network functions as follows: The carboxylate side chain of Asp-32 hydrogen bonds to a nitrogen-bonded proton on His-64's imidazole ring. This is possible because Asp is negatively charged at physiological pH. The other nitrogen on His-64 hydrogen bonds to the O-H proton of Ser-221. This last interaction results in charge-separation of O-H, with the oxygen atom being more nucleophilic. This allows the oxygen atom of Ser-221 to attack incoming substrates (ie. peptide bonds), assisted by a neighboring carboxyamide side chain of Asn-155.

Even though Asp-32, His-64, and Ser-221 are sequentially far apart, they converge in the 3D structure to form the active site.

To summarize the interactions described above, Ser-221 acts as a nucleophile and cleaves peptide bonds with its partially negative oxygen atom. This is possible due to the nature of the charge-relay site of subtilisin.

References

Deber, C.M. (Lecturer). (2006, Sep. 29). BCH210H1F. [Lecture]. Toronto: University of Toronto.


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Acknowledgement and Attribution Regarding Sources of Content

Some of the initial content on this page may be incorporated in part from copyleft sources in the public domain including wikis such as Wikipedia and AskDrWiki. Drug information for patients came from the The National Library of Medicine. Infectious disease information may have come from the Centers for Disease Control (CDC). Differential Diagnoses are drawn from clinicians as well as an amalgamation of 3 sources: 1.The Disease Database; 2. Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:3; 3. Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:7 .

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