Molecular Dynamics Study on Class A β-Lactamase: Hydrogen Bond Network among the Functional Groups of Penicillin G and Side Chains of the Conserved Residues in the Active Site

2003 ◽  
Vol 107 (37) ◽  
pp. 10274-10283 ◽  
Author(s):  
Yasuyuki Fujii ◽  
Noriaki Okimoto ◽  
Masayuki Hata ◽  
Tetsu Narumi ◽  
Kenji Yasuoka ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Hydrogen Bond ◽  
Functional Groups ◽  
Active Site ◽  
Penicillin G ◽  
Side Chains ◽  
Hydrogen Bond Network ◽  
Conserved Residues ◽  
Class A ◽  
Bond Network

scholarly journals A conserved hydrogen-bond network in the catalytic centre of animal glutaminyl cyclases is critical for catalysis

2008 ◽  
Vol 411 (1) ◽  
pp. 181-190 ◽  
Author(s):  
Kai-Fa Huang ◽  
Yu-Ruei Wang ◽  
En-Cheng Chang ◽  
Tsung-Lin Chou ◽  
Andrew H.-J. Wang
Keyword(s):  
Hydrogen Bond ◽  
Steady State ◽  
Active Site ◽  
Single Mutation ◽  
Hydrogen Bond Network ◽  
Conserved Residues ◽  
Km Value ◽  
Catalytic Role ◽  
Bond Network ◽  
Aspartic Peptidases

QCs (glutaminyl cyclases; glutaminyl-peptide cyclotransferases, EC 2.3.2.5) catalyse N-terminal pyroglutamate formation in numerous bioactive peptides and proteins. The enzymes were reported to be involved in several pathological conditions such as amyloidotic disease, osteoporosis, rheumatoid arthritis and melanoma. The crystal structure of human QC revealed an unusual H-bond (hydrogen-bond) network in the active site, formed by several highly conserved residues (Ser160, Glu201, Asp248, Asp305 and His319), within which Glu201 and Asp248 were found to bind to substrate. In the present study we combined steady-state enzyme kinetic and X-ray structural analyses of 11 single-mutation human QCs to investigate the roles of the H-bond network in catalysis. Our results showed that disrupting one or both of the central H-bonds, i.e., Glu201···Asp305 and Asp248···Asp305, reduced the steady-state catalysis dramatically. The roles of these two COOH···COOH bonds on catalysis could be partly replaced by COOH···water bonds, but not by COOH···CONH2 bonds, reminiscent of the low-barrier Asp···Asp H-bond in the active site of pepsin-like aspartic peptidases. Mutations on Asp305, a residue located at the centre of the H-bond network, raised the Km value of the enzyme by 4.4–19-fold, but decreased the kcat value by 79–2842-fold, indicating that Asp305 primarily plays a catalytic role. In addition, results from mutational studies on Ser160 and His319 suggest that these two residues might help to stabilize the conformations of Asp248 and Asp305 respectively. These data allow us to propose an essential proton transfer between Glu201, Asp305 and Asp248 during the catalysis by animal QCs.

scholarly journals Rhomboids make do with a weak hydrogen bond

2019 ◽  
Vol 151 (3) ◽  
pp. 274-274 ◽  
Author(s):  
Caitlin Sedwick
Keyword(s):  
Hydrogen Bond ◽  
Active Site ◽  
Hydrogen Bond Network ◽  
Weak Hydrogen Bond ◽  
Bond Network

JGP paper explores the strength of the hydrogen bond network at the active site of GlpG.

Reversible Hydrogen Bond Network Dynamics: Molecular Dynamics Simulations of Calix[4]arene-Catenanes

2011 ◽  
Vol 115 (20) ◽  
pp. 6445-6454 ◽  
Author(s):  
Thomas Schlesier ◽  
Thorsten Metzroth ◽  
Andreas Janshoff ◽  
Jürgen Gauss ◽  
Gregor Diezemann
Keyword(s):  
Molecular Dynamics ◽  
Hydrogen Bond ◽  
Molecular Dynamics Simulations ◽  
Network Dynamics ◽  
Hydrogen Bond Network ◽  
Bond Network ◽  
Dynamics Simulations

scholarly journals Characterizing Hydropathy of Amino Acid Side Chain in a Protein Environment by Investigating the Structural Changes of Water Molecules Network

2021 ◽  
Vol 8 ◽  
Author(s):  
Lorenzo Di Rienzo ◽  
Mattia Miotto ◽  
Leonardo Bò ◽  
Giancarlo Ruocco ◽  
Domenico Raimondo ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Hydrogen Bond ◽  
Amino Acid ◽  
Computational Method ◽  
Side Chain ◽  
Water Molecules ◽  
Amino Acid Side Chain ◽  
Hydrogen Bond Network ◽  
Bond Network ◽  
Protein Environment

Assessing the hydropathy properties of molecules, like proteins and chemical compounds, has a crucial role in many fields of computational biology, such as drug design, biomolecular interaction, and folding prediction. Over the past decades, many descriptors were devised to evaluate the hydrophobicity of side chains. In this field, recently we likewise have developed a computational method, based on molecular dynamics data, for the investigation of the hydrophilicity and hydrophobicity features of the 20 natural amino acids, analyzing the changes occurring in the hydrogen bond network of water molecules surrounding each given compound. The local environment of each residue is complex and depends on the chemical nature of the side chain and the location in the protein. Here, we characterize the solvation properties of each amino acid side chain in the protein environment by considering its spatial reorganization in the protein local structure, so that the computational evaluation of differences in terms of hydropathy profiles in different structural and dynamical conditions can be brought to bear. A set of atomistic molecular dynamics simulations have been used to characterize the dynamic hydrogen bond network at the interface between protein and solvent, from which we map out the local hydrophobicity and hydrophilicity of amino acid residues.

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