Distinguishing two groups of flavin reductases by analyzing the protonation state of an active site carboxylic acid

2011 ◽  
Vol 79 (7) ◽  
pp. 2076-2085 ◽  
Author(s):  
Verónica I. Dumit ◽  
Néstor Cortez ◽  
G. Matthias Ullmann
Keyword(s):  
Carboxylic Acid ◽  
Active Site ◽  
Protonation State

scholarly journals How Active-Site Protonation State Influences the Reactivity and Ligation of the Heme in Chlorite Dismutase

2010 ◽  
Vol 132 (16) ◽  
pp. 5711-5724 ◽  
Author(s):  
Bennett R. Streit ◽  
Béatrice Blanc ◽  
Gudrun S. Lukat-Rodgers ◽  
Kenton R. Rodgers ◽  
Jennifer L. DuBois
Keyword(s):  
Active Site ◽  
Protonation State ◽  
Chlorite Dismutase

scholarly journals Inhibition of Phosphodiesterase 5 Enzyme by Pterine- 6 Carboxylic Acid from Baphia nitida –Related to Erectile Dysfunction: Computational Kinetic

2020 ◽  
pp. 49-55
Author(s):  
Wopara, Iheanyichukwu ◽  
S. K. Mobisson ◽  
Egelege Aziemeola Pius ◽  
A. A. Uwakwe ◽  
M. O. Wegwu
Keyword(s):  
Erectile Dysfunction ◽  
Carboxylic Acid ◽  
Active Site ◽  
In Silico ◽  
Binding Pocket ◽  
Docking Studies ◽  
Drug Candidate ◽  
In Silico Docking ◽  
In Silico Studies ◽  
Phosphodiesterase 5

Treatment of erectile dysfunction is associated with inhibition of Phosphodiesterase 5 enzyme. This study deals with the evaluation of Pterin-6-carboxylic acid inhibitory activity on phosphodiesterase 5 (PDB ID: 4OEW) using in silico docking studies. Pterin-6-carboxylic acid from Baphia nitida was isolated using GC-MS and docked into PDE5 active site. The docking result showed that pterin-6-carboxylic acid bind to the active site of phosphodiesterase 5 with the binding energy value of -7.1 and 2.05A° - 2.23A° when compared with other compound found in the plant. Moreso, docking analysis with the ligand identified specific residues such as: Ile 778, Phe 820, Gln 817, Ser 815 and Gln 775 within the binding pocket which played an important role in the ligand binding affinity to the protein. Result from our In silico studies hypothesized that pterin-6-carboxylic acid can be an inhibitory agent for PDE5 protein which could be a potential drug candidate for the treatment of erectile dysfunction.

scholarly journals X-ray crystallographic studies on the hydrogen isotope effects of green fluorescent protein at sub-ångström resolutions

2019 ◽  
Vol 75 (12) ◽  
pp. 1096-1106 ◽  
Author(s):  
Yang Tai ◽  
Kiyofumi Takaba ◽  
Yuya Hanazono ◽  
Hoang-Anh Dao ◽  
Kunio Miki ◽  
...  
Keyword(s):  
Green Fluorescent Protein ◽  
Active Site ◽  
Hydrogen Isotope ◽  
Fluorescent Protein ◽  
Isotope Effects ◽  
Protonation State ◽  
X Ray ◽  
Two Samples ◽  
Deuterated Proteins ◽  
Green Fluorescent

Hydrogen atoms are critical to the nature and properties of proteins, and thus deuteration has the potential to influence protein function. In fact, it has been reported that some deuterated proteins show different physical and chemical properties to their protiated counterparts. Consequently, it is important to investigate protonation states around the active site when using deuterated proteins. Here, hydrogen isotope effects on the S65T/F99S/M153T/V163A variant of green fluorescent protein (GFP), in which the deprotonated B form is dominant at pH 8.5, were investigated. The pH/pD dependence of the absorption and fluorescence spectra indicates that the protonation state of the chromophore is the same in protiated GFP in H2O and protiated GFP in D2O at pH/pD 8.5, while the pK a of the chromophore became higher in D2O. Indeed, X-ray crystallographic analyses at sub-ångström resolution revealed no apparent changes in the protonation state of the chromophore between the two samples. However, detailed comparisons of the hydrogen OMIT maps revealed that the protonation state of His148 in the vicinity of the chromophore differed between the two samples. This indicates that protonation states around the active site should be carefully adjusted to be the same as those of the protiated protein when neutron crystallographic analyses of proteins are performed.

scholarly journals Structural and Binding Analysis of Pyrimidinol Carboxylic Acid andN-Hydroxy Quinazolinedione HIV-1 RNase H Inhibitors

2011 ◽  
Vol 55 (6) ◽  
pp. 2905-2915 ◽  
Author(s):  
Eric B. Lansdon ◽  
Qi Liu ◽  
Stephanie A. Leavitt ◽  
Mini Balakrishnan ◽  
Jason K. Perry ◽  
...  
Keyword(s):  
Carboxylic Acid ◽  
Metal Ions ◽  
Active Site ◽  
Water Environment ◽  
Divalent Metal ◽  
Rnase H ◽  
Accurate Assessment ◽  
Divalent Metal Ions ◽  
Substrate State ◽  
Hiv 1

ABSTRACTHIV-1 RNase H breaks down the intermediate RNA-DNA hybrids during reverse transcription, requiring two divalent metal ions for activity. Pyrimidinol carboxylic acid andN-hydroxy quinazolinedione inhibitors were designed to coordinate the two metal ions in the active site of RNase H. High-resolution (1.4 Å to 2.1 Å) crystal structures were determined with the isolated RNase H domain and reverse transcriptase (RT), which permit accurate assessment of the metal and water environment at the active site. The geometry of the metal coordination suggests that the inhibitors mimic a substrate state prior to phosphodiester catalysis. Surface plasmon resonance studies confirm metal-dependent binding to RNase H and demonstrate that the inhibitors do not bind at the polymerase active site of RT. Additional evaluation of the RNase H site reveals an open protein surface with few additional interactions to optimize active-site inhibitors.

Compound I of Nitric Oxide Synthase:  The Active Site Protonation State

2007 ◽  
Vol 129 (11) ◽  
pp. 3182-3188 ◽  
Author(s):  
Kyung-Bin Cho ◽  
Etienne Derat ◽  
Sason Shaik
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Active Site ◽  
Protonation State ◽  
Compound I ◽  
Oxide Synthase
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