Sandbox Reserved 303
From Proteopedia
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==Function== | ==Function== | ||
| - | Thermolysin functions to catalyze both the | + | Thermolysin functions to catalyze both the cleavage and the synthesis of peptide bonds.<ref name ="Matthews" /> |
The zinc molecule present at the active site is essential for the enzyme's function. It exists in an approximate tetrahedral coordination, bound to three amino acids (HIS 142, HIS 146, GLU 166) and water. During its activity, an incoming substrate will displace this water molecule towards GLU 143. <ref name ="Matthews" /> GLU 143 is thought to help activate this same water molecule, which will attack the substrate.<ref name="Juers" /> | The zinc molecule present at the active site is essential for the enzyme's function. It exists in an approximate tetrahedral coordination, bound to three amino acids (HIS 142, HIS 146, GLU 166) and water. During its activity, an incoming substrate will displace this water molecule towards GLU 143. <ref name ="Matthews" /> GLU 143 is thought to help activate this same water molecule, which will attack the substrate.<ref name="Juers" /> | ||
Revision as of 22:51, 18 March 2011
| This Sandbox is Reserved from January 10, 2010, through April 10, 2011 for use in BCMB 307-Proteins course taught by Andrea Gorrell at the University of Northern British Columbia, Prince George, BC, Canada. |
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Contents |
Thermolysin
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| 1y3g, resolution 2.10Å () | |||||||||
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| Ligands: | , , , | ||||||||
| Non-Standard Residues: | |||||||||
| Activity: | Thermolysin, with EC number 3.4.24.27 | ||||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
is a protein that is isolated from the thermophile Bacillus thermoproteolyticus. [1] This protein is characterized by a remarkable stability under heat and protein denaturants. [2]
Structure
Thermolysin comes from the superfamily of metalloproteases and was one of the first metalloproteases to have its structure solved crystallographically.[3]
The structure does not contain any stabilizing disulfide bonds.[4] Instead, Thermolysin binds four calcium ions that are necessary for its thermal stability. These four ions increase the intrinsic thermostability of the protein and protect its surface loops against autolysis. [1]
One zinc ion is also present in the protein. This zinc ion is located at the active site of Thermolysin.[3]
Function
Thermolysin functions to catalyze both the cleavage and the synthesis of peptide bonds.[1]
The zinc molecule present at the active site is essential for the enzyme's function. It exists in an approximate tetrahedral coordination, bound to three amino acids (HIS 142, HIS 146, GLU 166) and water. During its activity, an incoming substrate will displace this water molecule towards GLU 143. [1] GLU 143 is thought to help activate this same water molecule, which will attack the substrate.[3]
The zinc ion activates the scissile amide bond towards attack by water and stabilizes the resulting tetrahedral intermediate.[3] The metal is able to react with a number of functional groups that act as inhibitors. Some of these groups include thiols, ketones, hydroxamic acids, anionic groups such as carboxylates ans phosphinates, and silanediols.[3] The design of metalloprotease inhibitors such as for thermolysin is a common pharmaceutical target.[3]
