Assessing protein structures with a non-local atomic interaction energy

Melo, Francisco S.; Feytmans, Ernest

doi:10.1006/jmbi.1998.1665

Cited by 467 publications

(366 citation statements)

References 32 publications

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“…3) using the SWISS-MODEL online server (Guex and Peitsch, 1997;Schwede et al, 2003;Arnold et al, 2006) and the NAC α -NAC β heterodimer as the template structure. We assessed packing quality of this TβNAC model using the atomic empirical mean force potential implemented in the program ANOLEA (Melo and Feytmans, 1998) and using the program Protein & Cell PROCHECK (Laskowski et al, 2005). The overall stereochemical quality was good, and energy environment for majority residues were favorable (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Crystal structures of NAC domains of human nascent polypeptide-associated complex (NAC) and its αNAC subunit

et al. 2010

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Nascent polypeptide associated complex (NAC) and its two isolated subunits, αNAC and βNAC, play important roles in nascent peptide targeting. We determined a 1.9 Å resolution crystal structure of the interaction core of NAC heterodimer and a 2.4 Å resolution crystal structure of αNAC NAC domain homodimer. These structures provide detailed information of NAC heterodimerization and αNAC homodimerization. We found that the NAC domains of αNAC and βNAC share very similar folding despite of their relative low identity of amino acid sequences. Furthermore, different electric charge distributions of the two subunits at the NAC interface provide an explanation to the observation that the heterodimer of NAC complex is more stable than the single subunit homodimer. In addition, we successfully built a βNAC NAC domain homodimer model based on homologous modeling, suggesting that NAC domain dimerization is a general property of the NAC family. These 3D structures allow further studies on structurefunction relationship of NAC.

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Section: Discussionmentioning

confidence: 99%

Crystal structures of NAC domains of human nascent polypeptide-associated complex (NAC) and its αNAC subunit

et al. 2010

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“…The ANOLEA mean force potential were used to evaluate the local quality of the structural models. 38 The stereochemical plausibility of the models was evaluated via comparisons of Ramachandran plots calculated for experimental and modeled data (Supplementary Information section, Figure S2). …”

Section: Methodsmentioning

confidence: 99%

The Role of the Conformational Dynamics of Glutathione S-Transferase Epsilon Class on Insecticide Resistance inAnopheles gambiae

Pontes¹,

Maia²,

Lima³

et al. 2016

Journal of the Brazilian Chemical Society

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Glutathione S-transferases (GSTs) are enzymes capable of metabolizing cytotoxic compounds. The enzyme AgGSTE2, member of epsilon class GSTs (GSTE), is the most important GST conferring resistance to dichloro-diphenyl-trichloroethane (DDT) in Anopheles gambiae. We have investigated the conformational dynamics of three GSTE variants (GSTE2, GSTE2-I114T/F120L, GSTE5) from A. gambiae. Large-scale motions of helices H2 and H4 and conformational transition of the C-terminal governs the opening of the G-site and is expected to affect substrate binding and product release. This structural rearrangement places Glu116 (Glu120 in GSTE5) close of the thiol group of the tripeptide glutathione (GSH) cofactor, making this residue a candidate to act as a base in the activation of DDT. The structural rearrangement is noticeable for AgGSTE2-F120L, which has been shown to confer increased DDT-resistance. The other variants exhibit a more subtle rearrangement. These findings corroborate the hypothesis that the increase of the conformational dynamics of GST Epsilon class isoforms from A. gambiae promotes higher DDTase activity.Keywords: molecular dynamics simulation, evolutional constraint, positive and negative selection, metabolic resistance, malaria vector IntroductionGlutathione transferases (EC 2.5.1.18) are highly promiscuous proteins where broad functional promiscuity co-exists with highly conserved structural fold. Glutathione S-transferases (GSTs) constitute a large family of cytosolic and membrane-bound proteins that catalyze the nucleophilic addition of the tripeptide glutathione (GSH) to a variety of electrophilic toxins and drugs (xenobiotics), leading to their excretion. 1,2 Lately, several other activities have also been associated with GSTs, including steroid and leukotriene biosynthesis, peroxide degradation, doublebond cis-trans isomerization, dehydroascorbate reduction, Michael addition, and noncatalytic ligand binding and transport activity. 3 These polymorphic enzymes belong to supergene families whose members are generated by punctual mutations, gene duplication and alternative splicing. 4 The GST family is subdivided into several classes accordingly to its occurrence in different taxa.The number of isoforms per class varies widely, ranging from one to forty. 4 A single GST isoform is capable of conjugating glutathione to several hydrophobic substrates. Such promiscuity when coupled with the large number of isozymes generates a large range of potential substrates.Insects exhibit at least six classes of GSTs (Sigma, Omega, Theta, Zeta, Delta and Epsilon) with the first four classes present in almost all living organisms. 4,5 The Epsilon and Delta classes are arthropod specific and some members of these classes have been associated to insecticide resistance in culicid vectors. 5,6 The metabolism of toxic compounds in insects is conducted by a series of enzymes from different phases and GSTs act in phase II. GSTs metabolize these compounds in two ways: one has been cited above (through GSH conjugation) and the oth...

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“…The RMSD values ranged from 0.506 Å to 2.457 Å. The final structure was further evaluated for stereo-chemical structural quality through various standard tools such as RAMPAGE [44], PROSA [53] and ANOLEA.…”

Section: Structure Validationmentioning

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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Assessing protein structures with a non-local atomic interaction energy

Cited by 467 publications

References 32 publications

Crystal structures of NAC domains of human nascent polypeptide-associated complex (NAC) and its αNAC subunit

Crystal structures of NAC domains of human nascent polypeptide-associated complex (NAC) and its αNAC subunit

The Role of the Conformational Dynamics of Glutathione S-Transferase Epsilon Class on Insecticide Resistance inAnopheles gambiae

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

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