A Computational Model for Predicting ADAM17 Substrate Specificity

2013 ◽  
Vol 740 ◽  
pp. 525-529
Author(s):  
Liu Sen ◽  
Dong Pei ◽  
Song Liu ◽  
Xiao Hong Ma
Keyword(s):  
Substrate Specificity ◽  
Ectodomain Shedding ◽  
Cleavage Sites ◽  
Substrate Selection ◽  
Necrosis Factor Alpha ◽  
Protein Substrates ◽  
Tace Inhibitors ◽  
Factor Alpha ◽  
Necrosis Factor ◽  
Selection Of

Tumor necrosis factor-alpha converting enzyme (TACE) is a membrane-anchored protein that releases the soluble forms of many proteins by a process called ectodomain shedding. TACE has been considered as a potential target in a lot of diseases in autoimmune diseases and in cancers recently. In spite a lot of protein substrates have been found these years for TACE, the substrate selection of TACE is still not known. In this paper, a TACE-peptide complex was constructed, and used for the prediction of substrate sequences and cleavage sites. The result could be useful for understanding the substrate specificity of TACE, and designing better TACE inhibitors in future.

Tumor Necrosis Factor Alpha Converting Enzyme (TACE) as Possible Therapeutic Target in SARS-CoV-2 Induced Acute Respiratory Distress Syndrome (ARDS)

2020 ◽  
Author(s):  
Joao Batista Junior
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Inflammatory Responses ◽  
Converting Enzyme ◽  
Necrosis Factor Alpha ◽  
Tace Inhibitors ◽  
Factor Alpha ◽  
Activity State ◽  
Necrosis Factor

<div>This study reveals, for the first time, that rosiglitazone and pioglitazone, two thiazolidinedione drugs already approved as therapeutic agents to treat type II diabetes, were found to bind favorably to tumor necrosis factor alpha converting enzyme catalytic site with highlighted binding features.</div><div><br></div>This study suggests that rosiglitazone and pioglitazone, acting as TACE inhibitors agents might avoid or attenuate the hyperexcitability proteolytic activity state of TACE, represent a new potential therapeutic approach to treat SARS-CoV-2 infection-associated severe systemic inflammatory responses observed among severely or critically ill SARS-CoV-2 patients and, consequently, to diminish severe inflammatory‐induced lung injury, ARDS development and death rates.<br><br>

scholarly journals Structure and functions of tumor necrosis factor-alpha converting enzyme.

2003 ◽  
Vol 50 (3) ◽  
pp. 625-645 ◽  
Author(s):  
Renata Mezyk ◽  
Monika Bzowska ◽  
Joanna Bereta
Keyword(s):  
Tumor Necrosis Factor ◽  
Substrate Specificity ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Converting Enzyme ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Structure And Functions ◽  
Necrosis Factor

Tumor necrosis factor-alpha converting enzyme (TACE) is the first described and best characterized secretase. In this review the structure and the possible roles for TACE are summarized. The substrate specificity and the regulation of TACE activity as well as redundancy and possible cooperations of distinct secretases are also discussed.

Tumor Necrosis Factor Alpha Converting Enzyme (TACE) as Possible Therapeutic Target in SARS-CoV-2 Induced Acute Respiratory Distress Syndrome (ARDS)

2020 ◽  
Author(s):  
Joao Batista Junior
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Inflammatory Responses ◽  
Converting Enzyme ◽  
Necrosis Factor Alpha ◽  
Tace Inhibitors ◽  
Factor Alpha ◽  
Activity State ◽  
Necrosis Factor

<div>This study reveals, for the first time, that rosiglitazone and pioglitazone, two thiazolidinedione drugs already approved as therapeutic agents to treat type II diabetes, were found to bind favorably to tumor necrosis factor alpha converting enzyme catalytic site with highlighted binding features.</div><div><br></div>This study suggests that rosiglitazone and pioglitazone, acting as TACE inhibitors agents might avoid or attenuate the hyperexcitability proteolytic activity state of TACE, represent a new potential therapeutic approach to treat SARS-CoV-2 infection-associated severe systemic inflammatory responses observed among severely or critically ill SARS-CoV-2 patients and, consequently, to diminish severe inflammatory‐induced lung injury, ARDS development and death rates.<br><br>

Substitution of methionine 435 with leucine, isoleucine, and serine in tumor necrosis factor alpha converting enzyme inactivates ectodomain shedding activity

2007 ◽  
Vol 85 (1) ◽  
pp. 141-149 ◽  
Author(s):  
Liliana Pérez ◽  
John E. Kerrigan ◽  
Xiaojin Li ◽  
Huizhou Fan
Keyword(s):  
Growth Factor ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Ectodomain Shedding ◽  
Converting Enzyme ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

Tumor necrosis factor alpha (TNF-α) converting enzyme (TACE) is a zinc metalloprotease that has emerged as a general sheddase, which is responsible for ectodomain release of numerous membrane proteins, including the proinflammatory cytokine TNF-α, the leukocyte adhesin l-selectin and epidermal growth factor receptor ligand-transforming growth factor α (TGF-α), and related family members. Structurally, TACE belongs to a large clan of proteases, designated the metzincins, because TACE possesses a conserved methionine (Met435), frequently referred to as the met-turn residue, in its active site. A vital role of this residue in the function of TACE is supported by the fact that cells expressing the M435I TACE variant are defective in ectodomain shedding. However, the importance of Met435 in TACE appears to be uncertain, since another metzincin, matrix metalloprotease-2, has been found to be enzymatically fully active with either leucine or serine in place of its met-turn residue. We constructed TACE mutants with leucine or serine in place of Met435 to further examine the role of the met-turn residue in TACE-mediated ectodomain cleavage. Similar to the M435I TACE mutant, both the M435L and M435S constructs are defective in cleaving transmembrane TNF-α, TGF-α, and l-selectin. Comparative modeling and dynamic computation detected structural perturbations, which resulted in higher energy, in the catalytic zinc complexes of the Met435 TACE mutants compared with that in the wild-type enzyme. Thus, Met435 serves to maintain the stability of the catalytic center of TACE for the hydrolysis of peptide bonds in substrates.

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