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Review
. 2018 Aug 13;23(8):2020.
doi: 10.3390/molecules23082020.

Computational Molecular Docking and X-ray Crystallographic Studies of Catechins in New Drug Design Strategies

Shogo Nakano  1 , Shin-Ichi Megro  2 , Tadashi Hase  3 , Takuji Suzuki  4 , Mamoru Isemura  5 , Yoriyuki Nakamura  6 , Sohei Ito  7
Affiliations
Review

Computational Molecular Docking and X-ray Crystallographic Studies of Catechins in New Drug Design Strategies

Shogo Nakano et al. Molecules. .

Abstract

Epidemiological and laboratory studies have shown that green tea and green tea catechins exert beneficial effects on a variety of diseases, including cancer, metabolic syndrome, infectious diseases, and neurodegenerative diseases. In most cases, (-)-epigallocatechin gallate (EGCG) has been shown to play a central role in these effects by green tea. Catechins from other plant sources have also shown health benefits. Many studies have revealed that the binding of EGCG and other catechins to proteins is involved in its action mechanism. Computational docking analysis (CMDA) and X-ray crystallographic analysis (XCA) have provided detailed information on catechin-protein interactions. Several of these studies have revealed that the galloyl moiety anchors it to the cleft of proteins through interactions with its hydroxyl groups, explaining the higher activity of galloylated catechins such as EGCG and epicatechin gallate than non-galloylated catechins. In this paper, we review the results of CMDA and XCA of EGCG and other plant catechins to understand catechin-protein interactions with the expectation of developing new drugs with health-promoting properties.

Keywords: EGCG; X-ray crystallographic analysis; computational molecular docking analysis; green tea catechins.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Chemical structures of catechin-related compounds.
Figure 2
Figure 2
CMDA of EGCG binding to bovine SA. Interaction of EGCG with Trp134 (A) and Trp213 (B) are shown. Green broken arrows represent hydrogen bonding. The gallate group forms a hydrophobic bond with Trp213 (B). Cited from [12] under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike License.
Figure 3
Figure 3
CMDA of complexes of trypsin and catechins. Representative complex structures for trypsine complex with EGCG (A) and catechin (B). EGCG and catechin are shown as ball-and-stick and trypsine as cartoon. Data are cited from a literature of Shi et al. [14]. Adapted with permission of Copyright (2017) American Chemical Society.
Figure 4
Figure 4
MCDA of binding interactions of PKCδ. Phorbol ester (A) and gallic acid (B) bind to the similar sites in PKCδ. Reproduced from [25] under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike License.
Figure 5
Figure 5
CMDA of a β-catenine-catechin complex. Green dotted lines and orange lines represent hydrogen bond and π interactions, respectively. Reproduced from [29] under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike License.
Figure 6
Figure 6
CMDA of binding interactions of selected compounds including EGCG with the DH2 domain of STAT3. (A) BP1102; (B) gingektin; (C) withaferin A; (D) EGCG. The amino acids with hydrogen bond interactions are shown in bold. Reproduced from [40] under a Creative Commons Attribution 3.0 License. PII: 17,466.
Figure 7
Figure 7
CMDA of the binding of EGCG with serum immunoglobulin light chains to cause fibril formation. A filled circle represents an EGCG molecule. Data are reproduced from Hora et al. [71] under a Creative Commons Attribution 4.0 International License.
Figure 8
Figure 8
Autodock blind-docking of EGCG and EGC to SEA protein. Ligplot and docking simulation for the binding of EGCG to the active site of the A-6 region (A,B) and for the binding of EGC to the same region (C). The gallate moiety participates in the hydrogen bonding with Tyr 91 (A,B), while the A ring does so in EGC (C). Data are reproduced from Shimamura et al. [89] under the Creative Commons Attribution License.
Figure 9
Figure 9
CMDA of the binding interaction of EGCG with PLY (A) and SrtA (B). CMDA predicts the involvement of Ser256, Glu277, Tyr358, and Arg359 in PLY and Thr167, Lys169, and Phe237 in SrtA in the binding to EGCG. Reproduced from [91] under the terms of the Creative Commons Attribution License (CC BY).
Figure 10
Figure 10
Representative interactions of EGCG or ECG with proteins as revealed by XCA. (A): Ara h 8 complex with EC. The residues that form hydrophobic interactions are not displayed. (B): Leucoanthocyanidin reductase complex with (+)-catechin and NADPH. The residues that form hydrophobic interactions are not displayed. The nicotinamide and the C ring of ECG stack in parallel. (C): Soybean lipoxygenase-3 complex with iron and ECG. The residues that form hydrophobic interactions are also displayed in a wire-frame model. Hydrophobic contact is defined by the number of atoms within 3.9 Å of the ligands. (D): PA endonuclease complex with EGCG. Extensive hydrogen bonds observed in PA endonuclease. The residues that form hydrophobic interactions are not displayed. The red dotted lines represent the observed hydrogen bonds (within 3.3 Å). The blue dotted lines represent bridged hydrogen bonds. Figures were prepared using RCSB PDB Ligand Explorer software.
Figure 11
Figure 11
EGCG-binding to the surface of proteins. XCA of the interaction with PA endonuclease, troponin, Pin 1, and transthyretin. Figures are prepared using RCSB PDB Ligand Explorer software.
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