Identification of Active Site Residues in a Ferulic Acid Esterase (FAE-III) from Aspergillus niger

1998 ◽  
Vol 26 (2) ◽  
pp. S164-S164
Author(s):  
FRAJ O ALIWAN ◽  
GARY WILLIAMSON
Keyword(s):  
Aspergillus Niger ◽  
Ferulic Acid ◽  
Active Site ◽  
Active Site Residues ◽  
Ferulic Acid Esterase

Invertase from Hyper Producer Strain of Aspergillus niger: Physiochemical Properties, Thermodynamics and Active Site Residues Heat of Ionization

2009 ◽  
Vol 16 (9) ◽  
pp. 1098-1105 ◽  
Author(s):  
Habibullah Nadeem ◽  
Muhammad Rashid ◽  
Muhammad Riaz ◽  
Bibi Asma ◽  
Muhammad Javed ◽  
...  
Keyword(s):  
Aspergillus Niger ◽  
Active Site ◽  
Active Site Residues ◽  
Producer Strain ◽  
Physiochemical Properties

Esterification of ferulic acid with polyols using a ferulic acid esterase from Aspergillus niger

2006 ◽  
Vol 1760 (7) ◽  
pp. 1071-1079 ◽  
Author(s):  
Moriyasu Tsuchiyama ◽  
Tatsuji Sakamoto ◽  
Tomoyuki Fujita ◽  
Shuichi Murata ◽  
Haruhiko Kawasaki
Keyword(s):  
Aspergillus Niger ◽  
Ferulic Acid ◽  
Ferulic Acid Esterase

A ternary complex of hydroxycinnamoyl-CoA hydratase–lyase (HCHL) with acetyl-CoA and vanillin gives insights into substrate specificity and mechanism

2008 ◽  
Vol 414 (2) ◽  
pp. 281-289 ◽  
Author(s):  
Joseph P. Bennett ◽  
Lucille Bertin ◽  
Benjamin Moulton ◽  
Ian J. S. Fairlamb ◽  
A. Marek Brzozowski ◽  
...  
Keyword(s):  
Substrate Specificity ◽  
Ferulic Acid ◽  
Active Site ◽  
Three Dimensional ◽  
Alcohol Oxidase ◽  
Phenolic Hydroxyl ◽  
Vanillyl Alcohol ◽  
Active Site Residues ◽  
Acetyl Coa ◽  
Fragrance Compound

HCHL (hydroxycinnamoyl-CoA hydratase–lyase) catalyses the biotransformation of feruloyl-CoA to acetyl-CoA and the important flavour–fragrance compound vanillin (4-hydroxy-3-methoxybenzaldehyde) and is exploited in whole-cell systems for the bioconversion of ferulic acid into natural equivalent vanillin. The reaction catalysed by HCHL has been thought to proceed by a two-step process involving first the hydration of the double bond of feruloyl-CoA and then the cleavage of the resultant β-hydroxy thioester by retro-aldol reaction to yield the products. Kinetic analysis of active-site residues identified using the crystal structure of HCHL revealed that while Glu-143 was essential for activity, Ser-123 played no major role in catalysis. However, mutation of Tyr-239 to Phe greatly increased the KM for the substrate ferulic acid, fulfilling its anticipated role as a factor in substrate binding. Structures of WT (wild-type) HCHL and of the S123A mutant, each of which had been co-crystallized with feruloyl-CoA, reveal a subtle helix movement upon ligand binding, the consequence of which is to bring the phenolic hydroxyl of Tyr-239 into close proximity to Tyr-75 from a neighbouring subunit in order to bind the phenolic hydroxyl of the product vanillin, for which electron density was observed. The active-site residues of ligand-bound HCHL display a remarkable three-dimensional overlap with those of a structurally unrelated enzyme, vanillyl alcohol oxidase, that also recognizes p-hydroxylated aromatic substrates related to vanillin. The data both explain the observed substrate specificity of HCHL for p-hydroxylated cinnamate derivatives and illustrate a remarkable convergence of the molecular determinants of ligand recognition between the two otherwise unrelated enzymes.

Development of Xanthine Based Inhibitors Targeting Phosphodiesterase 9A

2017 ◽  
Vol 14 (10) ◽  
pp. 1122-1137 ◽  
Author(s):  
Nivedita Singh ◽  
Parameswaran Saravanan ◽  
M.S. Thakur ◽  
Sanjukta Patra
Keyword(s):  
Free Energy ◽  
Active Site ◽  
Signal Transduction Pathway ◽  
Docking Study ◽  
Primary Objective ◽  
Cgmp Level ◽  
Active Site Residues ◽  
Aromatic Fragment ◽  
Docking Approach ◽  
Free Energy Of Binding

Background: Phosphodiesterases 9A (PDE9A) is one of the prominent regulating enzymes of the signal transduction pathway having highest catalytic affinity for second messenger, cGMP. When the cGMP level is lowered, an uncontrolled expression of PDE9A may lead to various neurodegenerative diseases. To regulate the catalytic activity of PDE9A, potent inhibitors are needed. Objective: The primary objective of the present study was to develop new xanthine based inhibitors targeting PDE9A. This study was an attempt to bring structural diversification in PDE9A inhibitor development because most of the existing inhibitors are constructed over pyrazolopyrimidinone scaffold. Methods: Manual designing and parallel molecular docking approach were used for the development of xanthine derivatives. In this study, N1, N3, N9 and C8 positions of xanthine scaffold were selected as substitution sites to design 200 new compounds. Reverse docking and pharmaceutical analyses were used for final validation of most promising compounds. Results: By keeping free energy of binding cut-off of -6.0 kcal/mol, 52 compounds were screened. The compounds with substitution at N1, N3 and C8 positions of xanthine showed good occupancy in PDE9A active site pocket with a significant interaction pattern. This was further validated by screening different factors such as free energy of binding, inhibition constant and interacting active site residues in the 5Å region. Substitution at C8 position with phenyl substituent determined the inhibition affinity of compounds towards PDE9A by establishing a strong hydrophobic - hydrophobic interaction. The alkyl chain at N1 position generated selectivity of compounds towards PDE9A. The aromatic fragment at N3 position increased the binding affinity of compounds. Thus, by comparative docking study, it was found that compound 39-42 formed selective interaction towards PDE9A over other members of the PDE superfamily. Conclusion: From the present study, N1, N3 and C8 positions of xanthine were concluded as the best sites for substitution for the generation of potent PDE9A inhibitors.

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