ModBase, a database of annotated comparative protein structure models, and associated resources

Pieper, Ursula; Eswar, Narayanan; Webb, Ben; Eramian, David; Kelly, Libusha; Barkan, David T.; Carter, Hannah; Mankoo, Parminder K.; Karchin, Rachel; Martí‐Renom, Marc A.; Davis, Fred P.; Šali, Andrej

doi:10.1093/nar/gkq1091

Cited by 622 publications

(350 citation statements)

References 122 publications

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“…MODBASE is a queryable database of annotated protein structures models, theoretically calculated models, which may contain significant errors, not experimentally determined structures [13]. Published protein structures were edited, to remove HETATM by using Discovery Studio Visualizer (Version 2.5.5).…”

Section: Methodsmentioning

confidence: 99%

Molecular Docking of Known Carcinogen 4-(Methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) with Cyclin Dependent Kinases towards Its Potential Role in Cell Cycle Perturbation

et al. 2014

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Cell cycle is maintained almost all the times and is controlled by various regulatory proteins and their complexes (Cdk+Cyclin) in different phases of interphase (G1, S and G2) and mitosis of cell cycle. A number of mechanisms have been proposed for the initiation and progression of carcinogenesis by abruption in cell cycle process. One of the important features of cancer/carcinogenesis is functional loss of these cell cycle regulatory proteins particularly in CDKs and cyclins. We hypothesize that there is a direct involvement of these cell cycle regulatory proteins not only at the genetic level but also proteins level, during the initiation of carcinogenesis. Therefore, it becomes significant to determine inconsistency in the functioning of regulatory proteins due to interaction with carcinogen 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Hence, we investigated the interaction efficiency of NNK, against cell cycle regulatory proteins. We found a different value of ΔG (free energy of binding) among the studied proteins ranging between -3.29 to -7.25 kcal/mol was observed. To validate the results, we considered Human Oxy-Hemoglobin at 1.25 Å Resolution, [PDB_ID:1HHO] as a +ve control, (binding energy -6.06 kcal/mol). Finally, the CDK8 (PDB_ID:3RGF) and CDK2 (PDB_ID:3DDP) regulatory proteins showing significantly strong molecular interaction with NNK -7.25 kcal/mol, -6.19 kcal/mol respectively were analyzed in details. In this study we predicted that CDK8 protein fails to form functional complex with its complementary partner cyclin C in presence of NNK. Consequently, inconsistency of functioning in regulatory proteins might lead to the abruption in cell cycle progression; contribute to the loss of cell cycle control and subsequently increasing the possibility of carcinogenesis.

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Section: Methodsmentioning

confidence: 99%

Molecular Docking of Known Carcinogen 4-(Methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) with Cyclin Dependent Kinases towards Its Potential Role in Cell Cycle Perturbation

et al. 2014

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“…Although the twist of the solenoid can vary, reconstructions of the curvature of the solenoid, the exposure of residues to solvent, and the orientation of amino acid side chains are usually very accurate [51]. From the models available at ModBase [52], we selected entry 3cigA (28% identity, see Supporting information) [53], which corresponds to the mouse Toll-like receptor 3, and models nearly the whole LRRD of LRRC8A (repeats 2-17 and the final C-tail). We used Consurf [54] to map the degree of evolutionary conservation onto this model (Fig.…”

Section: Lrrc8 Proteins May Form Hexameric Channelsmentioning

confidence: 99%

LRRC8 proteins share a common ancestor with pannexins, and may form hexameric channels involved in cell‐cell communication

2012

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Leucine-rich repeat-containing 8 (LRRC8) proteins are composed of four transmembrane helices and 17 leucine-rich repeats (LRR). Although LRRC8 proteins have been associated with important processes, like maturation of B cells or adipocyte differentiation, their biology and molecular function are largely unknown. We found that LRRC8 proteins originated from the combination of a pannexin and an LRR domain (most likely related to the SHOC2, LAP, RSU1 and LRRIQ4 protein families) before the diversification of chordates. We propose that, like pannexins, LRRC8 proteins form hexameric channels, which participate in cell-cell communication processes. According to the inferred topological model, and contrary to what was previously assumed, the six LRR domains are located in the cytoplasm, and could participate in the organisation of signalling cascades. By compiling available proteomics and gene expression data, and on the basis of the LRRC8 proposed hexameric channel structure, we present clues to the function of this family.

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“…The modeling server ModWeb (http://salilab.org /modweb), an integral module of ModBase (18,19), was used to create the three-dimensional structure of the human eEF2K domain. ModBase relies on the homology modeling package MODELLER (20).…”

Section: Methodsmentioning

confidence: 99%

A Conserved Loop in the Catalytic Domain of Eukaryotic Elongation Factor 2 Kinase Plays a Key Role in Its Substrate Specificity

Moore

Mota

Mikolajek

et al. 2014

Molecular and Cellular Biology

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Eukaryotic elongation factor 2 kinase (eEF2K) is the best-characterized member of the ␣-kinase family. Within this group, only eEF2K and myosin heavy chain kinases (MHCKs) have known substrates. Here we have studied the roles of specific residues, selected on the basis of structural data for MHCK A and TRPM7, in the function of eEF2K. Our data provide the first information regarding the basis of the substrate specificity of ␣-kinases, in particular the roles of residues in the so-called N/D loop, which appears to occupy a position in the structure of ␣-kinases similar to that of the activation loop in other kinases. Several mutations in the EEF2K gene occur in tumors, one of which (Arg303Cys) is at a highly conserved residue in the N/D loop. This mutation greatly enhances eEF2K activity and may be cytoprotective. Our data support the concept that the major autophosphorylation site (Thr348 in eEF2K) docks into a binding pocket to help create the kinase-competent conformation. This is similar to the situation for MHCK A and is consistent with this being a common feature of ␣-kinases.

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ModBase, a database of annotated comparative protein structure models, and associated resources

Cited by 622 publications

References 122 publications

Molecular Docking of Known Carcinogen 4-(Methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) with Cyclin Dependent Kinases towards Its Potential Role in Cell Cycle Perturbation

Molecular Docking of Known Carcinogen 4-(Methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) with Cyclin Dependent Kinases towards Its Potential Role in Cell Cycle Perturbation

LRRC8 proteins share a common ancestor with pannexins, and may form hexameric channels involved in cell‐cell communication

A Conserved Loop in the Catalytic Domain of Eukaryotic Elongation Factor 2 Kinase Plays a Key Role in Its Substrate Specificity

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