Role of Aromatic Side Chains in the Binding of Volatile General Anesthetics to a Four-α-Helix Bundle†

Biochemistry ◽  
2002 ◽  
Vol 41 (12) ◽  
pp. 4080-4087 ◽  
Author(s):  
Gavin A. Manderson ◽  
Jonas S. Johansson
Keyword(s):  
Side Chains ◽  
General Anesthetics ◽  
Helix Bundle ◽  
Α Helix ◽  
Aromatic Side Chains

scholarly journals Free Energy Landscape and Rate Estimation of the Aromatic Ring Flips in Basic Pancreatic Trypsin Inhibitor Using Metadynamics

2021 ◽  
Author(s):  
Pär Söderhjelm ◽  
Mandar Kulkarni
Keyword(s):  
Free Energy ◽  
Trypsin Inhibitor ◽  
Side Chain ◽  
Side Chains ◽  
Aromatic Residues ◽  
Basic Pancreatic Trypsin Inhibitor ◽  
Pancreatic Trypsin Inhibitor ◽  
Energy Surfaces ◽  
Aromatic Side Chains

Aromatic side-chains (phenylalanine and tyrosine) of a protein flip by 180° around the Cβ-Cγ axis (χ2 dihedral of side-chain) producing two symmetry-equivalent states. The ring-flip dynamics act as an NMR probe to understand local conformational fluctuations. Ring-flips are categorized as slow (ms onwards) or fast (ns to near ms) based on timescales accessible to NMR experiments. In this study, we investigated the ability of the infrequent metadynamics approach to discriminate between slow and fast ring-flips for eight individual aromatic side-chains (F4, Y10, Y21, F22, Y23, F33, Y35, F45) of basic pancreatic trypsin inhibitor (BPTI). Well-tempered metadynamics simulations were performed to observe ring-flipping free energy surfaces for all eight aromatic residues. The results indicate that χ2 as a standalone collective variable (CV) is not sufficient to classify fast and slow ring-flips. Most of the residues needed χ1 (N−Cχα) as a complementary CV, indicating the importance of librational motions in ring-flips. Multiple pathways and mechanisms were observed for residues F4, Y10, and F22. Recrossing events are observed for residues F22 and F33, indicating a possible role of friction effects in the ring-flipping. The results demonstrate the successful application of the metadynamics based approach to estimate ring-flip rates of aromatic residues in BPTI and identify certain limitations of the approach.

scholarly journals Role of Aromatic Side Chains in Amyloid β-Protein Aggregation

2012 ◽  
Vol 3 (12) ◽  
pp. 1008-1016 ◽  
Author(s):  
Risto Cukalevski ◽  
Barry Boland ◽  
Birgitta Frohm ◽  
Eva Thulin ◽  
Dominic Walsh ◽  
...  
Keyword(s):  
Protein Aggregation ◽  
Amyloid Β ◽  
Side Chains ◽  
Amyloid Β Protein ◽  
Β Protein ◽  
Aromatic Side Chains

On the Role of Aromatic Side Chains in the Photoactivation of BLUF Domains†

Biochemistry ◽  
2007 ◽  
Vol 46 (25) ◽  
pp. 7405-7415 ◽  
Author(s):  
Magdalena Gauden ◽  
Jeffrey S. Grinstead ◽  
Wouter Laan ◽  
Ivo H. M. van Stokkum ◽  
Marcela Avila-Perez ◽  
...  
Keyword(s):  
Side Chains ◽  
Aromatic Side Chains

Role of Aromatic Side Chains in the Folding and Thermodynamic Stability of Integral Membrane Proteins

2007 ◽  
Vol 129 (26) ◽  
pp. 8320-8327 ◽  
Author(s):  
Heedeok Hong ◽  
Sangho Park ◽  
Ricardo H. Flores Jiménez ◽  
Dennis Rinehart ◽  
Lukas K. Tamm
Keyword(s):  
Membrane Proteins ◽  
Thermodynamic Stability ◽  
Integral Membrane Proteins ◽  
Side Chains ◽  
Aromatic Side Chains

The role of aromatic side chains on the supramolecular hydrogelation of naphthalimide/dipeptide conjugates

2018 ◽  
Vol 42 (6) ◽  
pp. 4443-4449 ◽  
Author(s):  
Shu-Min Hsu ◽  
Rajan Deepan Chakravarthy ◽  
Hsun Cheng ◽  
Fang-Yi Wu ◽  
Tsung-Sheng Lai ◽  
...  
Keyword(s):  
Amino Acid ◽  
Side Chain ◽  
Side Chains ◽  
Amino Acid Side Chain ◽  
Aromatic Side Chains

This study demonstrates the influence of an amino-acid side chain of NI-dipeptides on supramolecular hydrogelation and biocompatibility.

The role of aromatic side-chains in amyloid growth and membrane interaction of the islet amyloid polypeptide fragment LANFLVH

2010 ◽  
Vol 40 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Danilo Milardi ◽  
Michele F. M. Sciacca ◽  
Matteo Pappalardo ◽  
Domenico M. Grasso ◽  
Carmelo La Rosa
Keyword(s):  
Islet Amyloid Polypeptide ◽  
Side Chains ◽  
Islet Amyloid ◽  
Membrane Interaction ◽  
Aromatic Side Chains

scholarly journals Role of Amino Acid Side Chains in Region 17–31 of Parathyroid Hormone (PTH) in Binding to the PTH Receptor

2006 ◽  
Vol 281 (43) ◽  
pp. 32485-32495 ◽  
Author(s):  
Thomas Dean ◽  
Ashok Khatri ◽  
Zhanna Potetinova ◽  
Gordon E. Willick ◽  
Thomas J. Gardella
Keyword(s):  
Parathyroid Hormone ◽  
Binding Affinity ◽  
Transmembrane Domain ◽  
Binding Domain ◽  
Side Chains ◽  
Extracellular Loop ◽  
Wild Type ◽  
Α Helix ◽  
Competition Assays

The principal receptor-binding domain (Ser17–Val31) of parathyroid hormone (PTH) is predicted to form an amphiphilic α-helix and to interact primarily with the N-terminal extracellular domain (N domain) of the PTH receptor (PTHR). We explored these hypotheses by introducing a variety of substitutions in region 17–31 of PTH-(1–31) and assessing, via competition assays, their effects on binding to the wild-type PTHR and to PTHR-delNt, which lacks most of the N domain. Substitutions at Arg20 reduced affinity for the intact PTHR by 200-fold or more, but altered affinity for PTHR-delNt by 4-fold or less. Similar effects were observed for Glu substitutions at Trp23, Leu24, and Leu28, which together form the hydrophobic face of the predicted amphiphilic α-helix. Glu substitutions at Arg25, Lys26, and Lys27 (which forms the hydrophilic face of the helix) caused 4–10-fold reductions in affinity for both receptors. Thus, the side chains of Arg20, together with those composing the hydrophobic face of the ligand's putative amphiphilic α-helix, contribute strongly to PTHR-binding affinity by interacting specifically with the N domain of the receptor. The side chains projecting from the opposite helical face contribute weakly to binding affinity by different mechanisms, possibly involving interactions with the extracellular loop/transmembrane domain region of the receptor. The data help define the roles that side chains in the binding domain of PTH play in the PTH-PTHR interaction process and provide new clues for understanding the overall topology of the bimolecular complex.

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