Probing the structure of human glucose transporter 2 and analysis of protein ligand interactions

Duddela, Srikanth; Sekhar, P. Nataraj; Padmavati, G. V.; Banerjee, Amit Kumar; Murty, Upadhyayula Suryanarayana

doi:10.1007/s00044-009-9234-4

Cited by 10 publications

(8 citation statements)

References 41 publications

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“…As mentioned previously, GLUT2 is able to move to the apical side to support glucose and fructose uptake at high luminal concentrations, as shown in Figure 4 a and Figure 4 b [ 101 , 102 , 103 ]. The crystal structure of hsGLUT2 is not identified yet, but it is proposed to consist of 524 amino acids and to possess 12 transmembrane segments, forming an aqueous pore [ 104 ] with two subunits [ 105 ]. The larger subunit is assumed to shape the active binding site.…”

Section: Transport Mechanisms and Binding Sites Of Intestinal Satumentioning

confidence: 99%

“…The larger subunit is assumed to shape the active binding site. Coordinating amino acids with glucose are S145, K146, P149, S150, L153, S233, L234, Y266, D267, T270, N274, R277, L452, C453, and Q455 [ 105 ]. Phloretin, whose structure is shown in Table 2 , is widely used in research studies as a relatively specific GLUT2 inhibitor [ 56 , 59 , 60 ].…”

Section: Transport Mechanisms and Binding Sites Of Intestinal Satumentioning

confidence: 99%

“…Additionally, the substance is able to impede translocation of GLUT2 [ 106 ]. Other potent but not specific inhibitors of GLUT2 are glipizide, dihydrochalcone, glaucine and phosphatidylcholine [ 105 ].…”

Section: Transport Mechanisms and Binding Sites Of Intestinal Satumentioning

confidence: 99%

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Intestinal Saturated Long-Chain Fatty Acid, Glucose and Fructose Transporters and Their Inhibition by Natural Plant Extracts in Caco-2 Cells

Schreck

Melzig

2018

Molecules

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The intestinal absorption of fatty acids, glucose and fructose is part of the basic requirements for the provision of energy in the body. High access of saturated long-chain fatty acids (LCFA), glucose and fructose can facilitate the development of metabolic diseases, particularly the metabolic syndrome and type-2 diabetes mellitus (T2DM). Research has been done to find substances which decelerate or inhibit intestinal resorption of these specific food components. Promising targets are the inhibition of intestinal long-chain fatty acid (FATP2, FATP4), glucose (SGLT1, GLUT2) and fructose (GLUT2, GLUT5) transporters by plant extracts and by pure substances. The largest part of active components in plant extracts belongs to the group of polyphenols. This review summarizes the knowledge about binding sites of named transporters and lists the plant extracts which were tested in Caco-2 cells regarding uptake inhibition.

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Section: Transport Mechanisms and Binding Sites Of Intestinal Satumentioning

confidence: 99%

Section: Transport Mechanisms and Binding Sites Of Intestinal Satumentioning

confidence: 99%

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Intestinal Saturated Long-Chain Fatty Acid, Glucose and Fructose Transporters and Their Inhibition by Natural Plant Extracts in Caco-2 Cells

Schreck

Melzig

2018

Molecules

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“…Obtained model was further refined and subjected to molecular dynamics simulations using strategy followed in our earlier work. [ 30 31 ]…”

Section: Methodsmentioning

confidence: 99%

Analyzing a potential drug target N-myristoyltransferase of Plasmodium falciparum through in silico approaches

Banerjee

Arora

Murty

2012

J Global Infect Dis

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Background:Despite concerted global efforts to combat malaria, malaria elimination is still a remote dream. Fast evolution rate of malarial parasite along with its ability to respond quickly to any drug resulting in partial or complete resistance has been a cause of concern among researcher communities.Materials and Methods:Molecular modeling approach was adopted to gain insight about the structure and various analyses were performed. Modeller 9v3, Protparam, Protscale, MEME, NAMD and other tools were employed for this study. PROCHECK and other tools were used for stereo-chemical quality evaluation.Results and Conclusion:It was observed during the course of study that this protein contains 32.2% of aliphatic amino acids among which Leucine (9.5%) is predominant. Theoretical pI of 8.39 identified the protein as basic in nature and most of the amino acids present in N-Myristoyltransferase are hydrophobic (46.1%). Secondary structure analysis shows predominance of alpha helices and random coils. Motif analyses revealed that this target protein contains 2 signature motifs, i.e., EVNFLCVHK and KFGEGDG. Apart from motif search, three-dimensional model was generated and validated and the stereo-chemical quality check confirmed that 97.7% amino acid residues fall in the core region of Ramachandran plot. Molecular dynamics simulation resulted in maximum 1.3 Å Root Mean Square Deviation (RMSD) between the initial structure and the trajectories obtained later on. The template and the target molecule has shown 1.5 Å RMSD for the C alpha trace. A docking study was also conducted with various ligand molecules among which specific benzofuran compounds turned out to be effective. This derived information will help in designing new inhibitor molecules for this target protein as well in better understanding the parasite protein.

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“…Comparative modeling or homology modeling is an alternate method that aid in deriving structural insight about protein in absence of experimentally derived structure. Homology modeling has been used successfully for providing structural information of key enzymes in various instances in important human pathogens in past [8][9][10][11][12][13][14][15][16][17]. The enzyme of Babesia has pronounced and significant differences with the human counterpart.…”

Section: Biomedical Research 2018; 29 (10): 2197-2214 Issn 0970-938x mentioning

confidence: 99%

Structural analysis of the Babesia microti thioredoxin reductase: a potential drug target for babesiosis treatment

Arora¹,

Banerjee²,

Narasu³

2018

biomedicalresearch

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Babesia microti, the causative agent of human babesiosis which was endemic in United States and parts of Europe with sporadic cases in other regions is expanding its geographical range. Being a common transfusion threat, Babesia has become a cause of concern in researchers and epidemiologists. Human babesiosis is now recognized as an emerging disease and gains more attention now than ever before. Thioredoxin reductase, a promising drug target in apicomplexan parasite has been validated in several species. This study focused on in-silico analysis of physicochemical properties, functional and structural aspects of thioredoxin reductase of B. microti. Comparative modeling approach was adopted for developing the three dimensional structural model of Thioredoxin reductase of Babesia microti. The model developed was found to be of reasonably good stereo-chemical quality by structure validation servers. This study will provide valuable insights about the function and structure of the enzyme thioredoxin reductase of B. microti and aid in developing effective chemotherapeutic agents for control and treatment of Babesia.

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Probing the structure of human glucose transporter 2 and analysis of protein ligand interactions

Cited by 10 publications

References 41 publications

Intestinal Saturated Long-Chain Fatty Acid, Glucose and Fructose Transporters and Their Inhibition by Natural Plant Extracts in Caco-2 Cells

Intestinal Saturated Long-Chain Fatty Acid, Glucose and Fructose Transporters and Their Inhibition by Natural Plant Extracts in Caco-2 Cells

Analyzing a potential drug target N-myristoyltransferase of Plasmodium falciparum through in silico approaches

Structural analysis of the Babesia microti thioredoxin reductase: a potential drug target for babesiosis treatment

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