Severity: Warning
Message: file_get_contents(https://...@gmail.com&api_key=61f08fa0b96a73de8c900d749fcb997acc09): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
Filename: helpers/my_audit_helper.php
Line Number: 143
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 143
Function: file_get_contents
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 209
Function: simplexml_load_file_from_url
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 994
Function: getPubMedXML
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3134
Function: GetPubMedArticleOutput_2016
File: /var/www/html/application/controllers/Detail.php
Line: 574
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
Line: 488
Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
Line: 316
Function: require_once
l-Gulonate dehydrogenase (GuDH) is a crucial enzyme in the non-phosphorylated sugar metabolism or glucuronate-xylulose (GX) pathway. Some naturally occurring compounds inhibit GuDH. Ascorbic acid is one of such inhibitors for GuDH. However, the exact mechanism by which ascorbic acid inhibits GuDH is still unknown. In this study, we try to investigate GuDH inhibition using computational approaches by generating a model for buffalo GuDH. We used this model to perform blind dockings of ascorbic acid to GuDH. Some docked conformations of ascorbic acid bind near Asp39 and have steric clashes with crystal structure conformation of NADH. To assess the dynamic stability of the GuDH-ascorbic acid complex, we performed six molecular dynamics simulations for GuDH, three each in its free form and in complex with ascorbic acid for 50 ns, to obtain 300 ns of trajectories in total. During the simulations, ascorbic acid interacted with several residues nearby Asp39. As Asp39 is an important residue for NADH binding and specificity, the interaction of ascorbic acid near Asp39 hinders further NADH binding and ultimately affects the enzymatic functioning of GuDH. In this study, we analyze these interactions between ascorbic acid and GuDH. Our analysis reveals novel details on the mechanism of GuDH inhibition by ascorbic acid.
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Source |
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http://dx.doi.org/10.1016/j.compbiolchem.2018.09.015 | DOI Listing |
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