scholarly journals Inhibition of ADAM17/TACE activity by zinc-chelating rye secalin-derived tripeptides and analogues

RSC Advances ◽  
2017 ◽  
Vol 7 (42) ◽  
pp. 26361-26369 ◽  
Author(s):  
M. Chinonye Udechukwu ◽  
Apollinaire Tsopmo ◽  
Hannah Mawhinney ◽  
Rong He ◽  
Petra C. Kienesberger ◽  
...  
Keyword(s):  
Hydrogen Bonds ◽  
Active Site ◽  
Hydrophobic Interactions ◽  
Zinc Coordination

Rye secalin-derived cysteine-containing tripeptides and analogues inhibited ADAM17 activity via active site zinc coordination, hydrogen bonds and hydrophobic interactions.

scholarly journals Discovery of [1,2,4]Triazole Derivatives as New Metallo-β-Lactamase Inhibitors

Molecules ◽  
2019 ◽  
Vol 25 (1) ◽  
pp. 56
Author(s):  
Chen Yuan ◽  
Jie Yan ◽  
Chen Song ◽  
Fan Yang ◽  
Chao Li ◽  
...  
Keyword(s):  
Public Health ◽  
Molecular Docking ◽  
Active Site ◽  
Inhibitory Concentration ◽  
Hydrophobic Interactions ◽  
Global Public Health ◽  
Triazole Derivatives ◽  
Potent Inhibition ◽  
Zinc Coordination

The emergence and spread of metallo-β-lactamase (MBL)-mediated resistance to β-lactam antibacterials has already threatened the global public health. A clinically useful MBL inhibitor that can reverse β-lactam resistance has not been established yet. We here report a series of [1,2,4]triazole derivatives and analogs, which displayed inhibition to the clinically relevant subclass B1 (Verona integron-encoded MBL-2) VIM-2. 3-(4-Bromophenyl)-6,7-dihydro-5H-[1,2,4]triazolo [3,4-b][1,3]thiazine (5l) manifested the most potent inhibition with an IC50 (half-maximal inhibitory concentration) value of 38.36 μM. Investigations of 5l against other B1 MBLs and the serine β-lactamases (SBLs) revealed the selectivity to VIM-2. Molecular docking analyses suggested that 5l bound to the VIM-2 active site via the triazole involving zinc coordination and made hydrophobic interactions with the residues Phe61 and Tyr67 on the flexible L1 loop. This work provided new triazole-based MBL inhibitors and may aid efforts to develop new types of inhibitors combating MBL-mediated resistance.

WHICH IS THE PROTON-SHUTTLE IN ISOXANTHOPTERIN DEAMINASE? QM/MM MD UNDERSTANDING

2013 ◽  
Vol 12 (08) ◽  
pp. 1341002 ◽  
Author(s):  
XIN ZHANG ◽  
MING LEI
Keyword(s):  
Crystal Structure ◽  
Molecular Dynamics ◽  
Hydrogen Bonds ◽  
Proton Transfer ◽  
Glutamic Acid ◽  
Active Site ◽  
Nucleophilic Attack ◽  
Zinc Ions ◽  
Initial Model ◽  
Dynamics Simulations

The deamination process of isoxanthopterin catalyzed by isoxanthopterin deaminase was determined using the combined QM(PM3)/MM molecular dynamics simulations. In this paper, the updated PM3 parameters were employed for zinc ions and the initial model was built up based on the crystal structure. Proton transfer and following steps have been investigated in two paths: Asp336 and His285 serve as the proton shuttle, respectively. Our simulations showed that His285 is more effective than Aap336 in proton transfer for deamination of isoxanthopterin. As hydrogen bonds between the substrate and surrounding residues play a key role in nucleophilic attack, we suggested mutating Thr195 to glutamic acid, which could enhance the hydrogen bonds and help isoxanthopterin get close to the active site. The simulations which change the substrate to pterin 6-carboxylate also performed for comparison. Our results provide reference for understanding of the mechanism of deaminase and for enhancing the deamination rate of isoxanthopterin deaminase.

scholarly journals Short hydrogen bonds in the catalytic mechanism of serine proteases

2008 ◽  
Vol 73 (4) ◽  
pp. 393-403 ◽  
Author(s):  
Vladimir Leskovac ◽  
Svetlana Trivic ◽  
Draginja Pericin ◽  
Mira Popovic ◽  
Julijan Kandrac
Keyword(s):  
Hydrogen Bond ◽  
Hydrogen Bonds ◽  
Active Site ◽  
Serine Proteases ◽  
Active Sites ◽  
Catalytic Mechanism ◽  
Data Bank ◽  
Ground State Structure ◽  
Low Barrier Hydrogen Bonds ◽  
Short Hydrogen Bonds

The survey of crystallographic data from the Protein Data Bank for 37 structures of trypsin and other serine proteases at a resolution of 0.78-1.28 ? revealed the presence of hydrogen bonds in the active site of the enzymes, which are formed between the catalytic histidine and aspartate residues and are on average 2.7 ? long. This is the typical bond length for normal hydrogen bonds. The geometric properties of the hydrogen bonds in the active site indicate that the H atom is not centered between the heteroatoms of the catalytic histidine and aspartate residues in the active site. Taken together, these findings exclude the possibility that short "low-barrier" hydrogen bonds are formed in the ground state structure of the active sites examined in this work. Some time ago, it was suggested by Cleland that the "low-barrier hydrogen bond" hypothesis is operative in the catalytic mechanism of serine proteases, and requires the presence of short hydrogen bonds around 2.4 ? long in the active site, with the H atom centered between the catalytic heteroatoms. The conclusions drawn from this work do not exclude the validity of the "low-barrier hydrogen bond" hypothesis at all, but they merely do not support it in this particular case, with this particular class of enzymes.

scholarly journals The Subtleties of Dissolution and Regeneration of Cellulose: Breaking and Making Hydrogen Bonds

BioResources ◽  
2015 ◽  
Vol 10 (3) ◽  
pp. 3811-3814 ◽  
Author(s):  
Björn Lindman ◽  
Bruno Medronho
Keyword(s):  
Hydrogen Bonding ◽  
Hydrogen Bonds ◽  
Hydrophobic Interactions ◽  
Cellulose Dissolution ◽  
Solution Behavior ◽  
Current Discussion ◽  
Scientific Controversies ◽  
A Current

Cellulose dissolution and regeneration are old topics that have recently gained renewed attention. This is reflected in both applications – earlier and novel – and in scientific controversies. There is a current discussion in the literature on the balance between hydrogen bonding and hydrophobic interactions in controlling the solution behavior of cellulose. Some of the key ideas are recalled.

scholarly journals Molecular docking and pharmacokinetic screening of eucalyptol (1,8 cineole) from eucalyptus essential oil against SARS-CoV-2

2020 ◽  
Vol 12 (3) ◽  
pp. 536-545
Author(s):  
Arun D. SHARMA ◽  
Inderjeet KAUR
Keyword(s):  
Molecular Docking ◽  
Essential Oil ◽  
Active Site ◽  
In Silico ◽  
Hydrophobic Interactions ◽  
Rna Virus ◽  
In Silico Analysis ◽  
Active Site Residues ◽  
Virus Family

SARS-CoV-2 (COVID-19), member of corona virus family, is a positive single stranded RNA virus. Due to lack of drugs it is spreading its tentacles across the world. Being associated with cough, fever, and respiratory distress, this disease caused more than 15% mortality worldwide. Mpro/3CLpro has recently been regarded as a suitable target for drug design due to its vital role in virus replication. The current study focused on the inhibitory activity of eucalyptol (1,8 cineole), an essential oil component from eucalyptus oil, against Mpro/3CLprofrom SARS-CoV-2. Till date there is no work is undertaken on in-silico analysis of this compound against Mpro/3CLproof SARS-CoV-2. Molecular docking studies were conducted by using 1-click dock tool and Patchdock analysis. In-silico absorption, distribution, metabolism, excretion and toxicity (ADMET) profile were also studied. The calculated parameters such as docking score indicated effective binding of eucalyptol to COVID-19 Mpro protein. Active site prediction revealed the involvement of active site residues in ligand binding. Interactions results indicated that, Mpro/3CLpro/eucalyptol complexes forms hydrophobic interactions. ADMET studies provided guidelines and mechanistic scope for identification of potent anti-COVID 19 drug. Therefore, eucalyptol may represent potential herbal treatment to act as COVID-19 Mpro/3CLproinhibitor, a finding which must be validated in vivo.

Quadruple hydrogen bonds and thermo-triggered hydrophobic interactions generate dynamic hydrogels to modulate transplanted cell retention

2019 ◽  
Vol 7 (4) ◽  
pp. 1286-1298 ◽  
Author(s):  
Sa Liu ◽  
Dawei Qi ◽  
Yunhua Chen ◽  
Lijing Teng ◽  
Yongguang Jia ◽  
...  
Keyword(s):  
Hydrogen Bonds ◽  
Hydrophobic Interactions ◽  
Cell Retention

Supramolecular dynamic hydrogels with quadruple hydrogen bonds and thermo-triggered hydrophobic interactions demonstrate a promising capability of modulating transplanted cell retention.

Models for the binding channel of wild type and mutant transthyretin with glabridin

RSC Advances ◽  
2016 ◽  
Vol 6 (99) ◽  
pp. 96816-96823 ◽  
Author(s):  
Liyun Zou ◽  
Jingxuan Zhu ◽  
Yang Dong ◽  
Weiwei Han ◽  
Yingjie Guo ◽  
...  
Keyword(s):  
Hydrogen Bonds ◽  
Hydrophobic Interactions ◽  
Wild Type ◽  
Binding Interface

Our results indicate that additional high-occupancy hydrogen bonds were observed at the binding interface between the two dimers in V30A TTR, while stabilisation hydrophobic interactions between residues in the mutant AB loop decreased.

Molecular docking and molecular dynamics simulations of fumarate hydratase and its mutant H235N complexed with pyromellitic acid and citrate

2017 ◽  
Vol 15 (06) ◽  
pp. 1750026 ◽  
Author(s):  
S. Subasri ◽  
Santosh Kumar Chaudhary ◽  
K. Sekar ◽  
Manish Kesherwani ◽  
D. Velmurugan
Keyword(s):  
Molecular Dynamics ◽  
Active Site ◽  
Model Building ◽  
Hydrophobic Interactions ◽  
Conformational Stability ◽  
Fumarate Hydratase ◽  
Md Simulations ◽  
Major Effect ◽  
Active Site Residues ◽  
Pyromellitic Acid

Fumarase catalyzes the reversible, stereospecific hydration/dehydration of fumarate to L-malate during the Kreb’s cycle. In the crystal structure of the tetrameric fumarase, it was found that some of the active site residues S145, T147, N188 G364 and H235 had water-mediated hydrogen bonding interactions with pyromellitic acid and citrate which help to the protonation state for the conversion of fumarate to malate. When His 235 is mutated with Asn (H235N), water-mediated interactions were lost due to the shifting of active site water molecule by 0.7 Å away. Molecular dynamics (MD) simulations were also carried out by NAMD and analyzed using Assisted Model Building with Energy Refinement (AMBER) program to better understand the conformational stability and other aspects during the binding of pyromellitic acid and citrate with native and mutant FH. The role of hydrogen bonds and hydrophobic interactions was also analyzed. The present study confirms that the H235N mutation has a major effect on the catalytic activity of fumarase which is evident from the biochemical studies.

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