Clustering of Aromatic Amino Acid Residues around Methionine in Proteins

Short-range, non-covalent interactions between amino acid residues determine protein structures and contribute to protein functions in diverse ways. The interactions of the thioether of methionine with the aromatic rings of tyrosine, tryptophan, and/or phenylalanine has long been discussed and such interactions are favorable on the order of 1–3 kcal mol−1. Here, we carry out a new bioinformatics survey of known protein structures where we assay the propensity of three aromatic residues to localize around the [-CH2-S-CH3] of methionine. We term these groups “3-bridge clusters”. A dataset consisting of 33,819 proteins with less than 90% sequence identity was analyzed and such clusters were found in 4093 structures (or 12% of the non-redundant dataset). All sub-classes of enzymes were represented. A 3D coordinate analysis shows that most aromatic groups localize near the CH2 and CH3 of methionine. Quantum chemical calculations support that the 3-bridge clusters involve a network of interactions that involve the Met-S, Met-CH2, Met-CH3, and the π systems of nearby aromatic amino acid residues. Selected examples of proposed functions of 3-bridge clusters are discussed.

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Non-Covalent Interactions Involving Aromatic Residues in Protein Structures: Stability and Dynamics in Membrane and Globular Proteins using Molecular Dynamics Simulations

Biophysical Journal ◽

10.1016/j.bpj.2009.12.3480 ◽

2010 ◽

Vol 98 (3) ◽

pp. 635a-636a

Author(s):

Alok Jain ◽

Ramasubbu Sankararamakrishnan

Keyword(s):

Molecular Dynamics ◽

Molecular Dynamics Simulations ◽

Protein Structures ◽

Globular Proteins ◽

Aromatic Residues ◽

Non Covalent Interactions ◽

Dynamics Simulations ◽

Covalent Interactions

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Configurational requirements of aromatic amino acid residues for the activity of PRP-hexapeptide

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19882583 ◽

1988 ◽

Vol 53 (11) ◽

pp. 2583-2590 ◽

Cited By ~ 2

Author(s):

Aleksandra Kubik ◽

Zbigniew Szewczuk ◽

Ignacy Z. Siemion ◽

Zbigniew Wieczorek ◽

Krystyna Spiegel ◽

...

Keyword(s):

Immune Response ◽

Biological Activity ◽

Amino Acid ◽

Aromatic Amino Acid ◽

Amino Acid Residues ◽

Aromatic Rings

The three analogues with D-amino acid substituents at position 1 and 5 of PRP-hexapeptide were synthesized and tested for its biological activity to check the influence of the spacial orientation of aromatic rings on the immune response. One of the analogs (Tyr-Val-Pro-Leu-D-Phe-Pro) was found to have the immunoregulatory activity.

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Statistical Force-Field for Structural Modeling Using Chemical Cross-Linking/mass Spectrometry Distance Constraints

10.26434/chemrxiv.6030563 ◽

2018 ◽

Author(s):

Allan J. R. Ferrari ◽

Fabio C. Gozzo ◽

Leandro Martinez

Keyword(s):

Mass Spectrometry ◽

Amino Acid ◽

Force Field ◽

Protein Structures ◽

Protein Structure Determination ◽

Structural Modeling ◽

Cross Linking ◽

Amino Acid Residues ◽

Distance Constraints ◽

Chemical Cross Linking

<div><p>Chemical cross-linking/Mass Spectrometry (XLMS) is an experimental method to obtain distance constraints between amino acid residues, which can be applied to structural modeling of tertiary and quaternary biomolecular structures. These constraints provide, in principle, only upper limits to the distance between amino acid residues along the surface of the biomolecule. In practice, attempts to use of XLMS constraints for tertiary protein structure determination have not been widely successful. This indicates the need of specifically designed strategies for the representation of these constraints within modeling algorithms. Here, a force-field designed to represent XLMS-derived constraints is proposed. The potential energy functions are obtained by computing, in the database of known protein structures, the probability of satisfaction of a topological cross-linking distance as a function of the Euclidean distance between amino acid residues. The force-field can be easily incorporated into current modeling methods and software. In this work, the force-field was implemented within the Rosetta ab initio relax protocol. We show a significant improvement in the quality of the models obtained relative to current strategies for constraint representation. This force-field contributes to the long-desired goal of obtaining the tertiary structures of proteins using XLMS data. Force-field parameters and usage instructions are freely available at http://m3g.iqm.unicamp.br/topolink/xlff <br></p></div><p></p><p></p>

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Non-Covalent Interactions with Aromatic Rings: Current Understanding and Implications for Rational Drug Design

Current Pharmaceutical Design ◽

10.2174/13816128113199990440 ◽

2013 ◽

Vol 19 (36) ◽

pp. 6522-6533 ◽

Cited By ~ 15

Author(s):

Shanshan Li ◽

Yuan Xu ◽

Qiancheng Shen ◽

Xian Liu ◽

Jing Lu ◽

...

Keyword(s):

Drug Design ◽

Rational Drug Design ◽

Current Understanding ◽

Aromatic Rings ◽

Rational Drug ◽

Non Covalent Interactions ◽

Covalent Interactions

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Synthesis, Characterization, and Non-Covalent Interactions of Palladium(II)-Amino Acid Complexes

Molecules ◽

10.3390/molecules26144331 ◽

2021 ◽

Vol 26 (14) ◽

pp. 4331

Author(s):

David B. Hobart ◽

Michael A. G. Berg ◽

Hannah M. Rogers ◽

Joseph S. Merola

Keyword(s):

Amino Acid ◽

High Resolution Mass Spectrometry ◽

Resonance Spectroscopy ◽

Spectroscopic Techniques ◽

X Ray Diffraction ◽

Amino Acid Complexes ◽

Acetone Water ◽

Square Planar ◽

Non Covalent Interactions ◽

Covalent Interactions

The reaction of palladium(II) acetate with acyclic amino acids in acetone/water yields square planar bis-chelated palladium amino acid complexes that exhibit interesting non-covalent interactions. In all cases, complexes were examined by multiple spectroscopic techniques, especially HRMS (high resolution mass spectrometry), IR (infrared spectroscopy), and 1H NMR (nuclear magnetic resonance) spectroscopy. In some cases, suitable crystals for single crystal X-ray diffraction were able to be grown and the molecular structure was obtained. The molecular geometries of the products are discussed. Except for the alanine complex, all complexes incorporate water molecules into the extended lattice and exhibit N-H···O and/or O···(HOH)···O hydrogen bonding interactions. The non-covalent interactions are discussed in terms of the extended lattice structures exhibited by the structures.

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