The role of ecotin dimerization in protease inhibition

Eggers, Christopher T.; Wang, Stephanie X.; Fletterick, Robert J.; Craik, Charles S.

doi:10.1006/jmbi.2001.4754

Cited by 41 publications

(45 citation statements)

References 69 publications

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“…These results are consistent with the literature regarding the mutation of the primary site where inhibition that occurs with ecotin-RR (Met84Arg and Met85Arg) improves its interactions with thrombin and a thrombin-like catalytic site using an in silico study and some in vitro enzymatic experiments [21]. It is important to emphasize that the IC 50 provide an apparent inhibition constant under the conditions described and these identical conditions were used for all inhibition studies, making them relative to one another and valid comparisons [37].…”

Section: Discussionsupporting

confidence: 83%

Ecotin: Exploring a feasible antithrombotic profile

Wermelinger

Frattani

Carneiro-Lobo

et al. 2015

International Journal of Biological Macromolecules

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Section: Discussionsupporting

confidence: 83%

Ecotin: Exploring a feasible antithrombotic profile

Wermelinger

Frattani

Carneiro-Lobo

et al. 2015

International Journal of Biological Macromolecules

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“…4A shows the protease inhibition assay results starting at 5 µg/ml concentration of HE-4 up to 50 µg/ml, and at 50 µg/ml concentration, it inhibits almost completely all the tested proteases. SLPI inhibits trypsin and chyomtrypsin with K i which is not markedly different for both of these proteases [40] while HE-4 has low affinity towards trypsin and considerably higher affinity towards chymotrypsin (Table 2) as determined by SPR. This highlights different inhibition profile for HE-4 and SLPI.…”

Section: Discussionmentioning

confidence: 90%

Human Epididymis Protein-4 (HE-4): A Novel Cross-Class Protease Inhibitor

et al. 2012

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Epididymal proteins represent the factors necessary for maturation of sperm and play a crucial role in sperm maturation. HE-4, an epididymal protein, is a member of whey acidic protein four-disulfide core (WFDC) family with no known function. A WFDC protein has a conserved WFDC domain of 50 amino acids with eight conserved cystine residue. HE-4 is a 124 amino acid long polypeptide with two WFDC domains. Here, we show that HE-4 is secreted in the human seminal fluid as a disulfide-bonded homo-trimer and is a cross-class protease inhibitor inhibits some of the serine, aspartyl and cysteine proteases tested using hemoglobin as a substrate. Using SPR we have also observed that HE-4 shows a significant binding with all these proteases. Disulfide linkages are essential for this activity. Moreover, HE-4 is N-glycosylated and highly stable on a wide range of pH and temperature. Taken together this suggests that HE-4 is a cross-class protease inhibitor which might confer protection against microbial virulence factors of proteolytic nature.

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“…In this way, the exosite actually makes the inhibitor less specific, or more capable of inhibiting a broad range of proteases, and allows one bacterial inhibitor to protect against a number of host proteases. [13] …”

Section: Competitive Inhibition With Exosite Bindingmentioning

confidence: 99%