Exploring the Molecular Basis for Binding of Inhibitors by Threonyl-tRNA Synthetase from Brucella abortus: A Virtual Screening Study

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Abstract

Targeting threonyl-tRNA synthetase (ThrRS) of Brucella abortus is a promising approach to developing small-molecule drugs against bovine brucellosis. Using the BLASTp algorithm, we identified ThrRS from Escherichia coli (EThrRS, PDB ID 1QF6), which is 51% identical to ThrRS from Brucella abortus (BaThrRS) at the amino acid sequence level. EThrRS was used as the template to construct a BaThrRS homology model which was optimized using molecular dynamics simulations. To determine the residues important for substrate ATP binding, we identified the ATP-binding regions of BaThrRS, docked ATP to the protein, and identified the residues whose side chains surrounded bound ATP. We then used the binding site of ATP to virtually screen for BaThrRS inhibitors and got seven leads. We further characterized the BaThrRS-binding site of the compound with the highest predicted inhibitory activity. Our results should facilitate future experimental effects to find novel drugs for use against bovine brucellosis.

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Most cited references 42

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CASTp: computed atlas of surface topography of proteins with structural and topographical mapping of functionally annotated residues

Joe Dundas, Zheng Ouyang, Jeffery Tseng … (2006)

Cavities on a proteins surface as well as specific amino acid positioning within it create the physicochemical properties needed for a protein to perform its function. CASTp () is an online tool that locates and measures pockets and voids on 3D protein structures. This new version of CASTp includes annotated functional information of specific residues on the protein structure. The annotations are derived from the Protein Data Bank (PDB), Swiss-Prot, as well as Online Mendelian Inheritance in Man (OMIM), the latter contains information on the variant single nucleotide polymorphisms (SNPs) that are known to cause disease. These annotated residues are mapped to surface pockets, interior voids or other regions of the PDB structures. We use a semi-global pair-wise sequence alignment method to obtain sequence mapping between entries in Swiss-Prot, OMIM and entries in PDB. The updated CASTp web server can be used to study surface features, functional regions and specific roles of key residues of proteins.

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Protein structure prediction and structural genomics.

D. Baker, A. Sali (2001)

Genome sequencing projects are producing linear amino acid sequences, but full understanding of the biological role of these proteins will require knowledge of their structure and function. Although experimental structure determination methods are providing high-resolution structure information about a subset of the proteins, computational structure prediction methods will provide valuable information for the large fraction of sequences whose structures will not be determined experimentally. The first class of protein structure prediction methods, including threading and comparative modeling, rely on detectable similarity spanning most of the modeled sequence and at least one known structure. The second class of methods, de novo or ab initio methods, predict the structure from sequence alone, without relying on similarity at the fold level between the modeled sequence and any of the known structures. In this Viewpoint, we begin by describing the essential features of the methods, the accuracy of the models, and their application to the prediction and understanding of protein function, both for single proteins and on the scale of whole genomes. We then discuss the important role that protein structure prediction methods play in the growing worldwide effort in structural genomics.

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A method to identify protein sequences that fold into a known three-dimensional structure.

R Lüthy, D Eisenberg, James Bowie (1991)

The inverse protein folding problem, the problem of finding which amino acid sequences fold into a known three-dimensional (3D) structure, can be effectively attacked by finding sequences that are most compatible with the environments of the residues in the 3D structure. The environments are described by: (i) the area of the residue buried in the protein and inaccessible to solvent; (ii) the fraction of side-chain area that is covered by polar atoms (O and N); and (iii) the local secondary structure. Examples of this 3D profile method are presented for four families of proteins: the globins, cyclic AMP (adenosine 3',5'-monophosphate) receptor-like proteins, the periplasmic binding proteins, and the actins. This method is able to detect the structural similarity of the actins and 70- kilodalton heat shock proteins, even though these protein families share no detectable sequence similarity.

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Author and article information

Contributors

Christo Z. Christov: Role: Academic Editor

Journal

Journal ID (nlm-ta): Int J Mol Sci

Journal ID (iso-abbrev): Int J Mol Sci

Journal ID (publisher-id): ijms

Title: International Journal of Molecular Sciences

Publisher: MDPI

ISSN (Electronic): 1422-0067

Publication date (Electronic): 19 July 2016

Publication date Collection: July 2016

Volume: 17

Issue: 7

Electronic Location Identifier: 1078

Affiliations

[1 ]Ministry of Agriculture Laboratory of Quality & Safety Risk Assessment for Dairy Products (Beijing), Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China; liming01@ 123456caas.cn (M.L.); wenfang@ 123456caas.cn (F.W.); zhaoshengguo1984@ 123456163.com (S.Z.); woaisanzang@ 123456126.com (P.W.); lisongli@ 123456caas.cn (S.L.); zhangyangdong@ 123456caas.cn (Y.Z.); wangjiaqi@ 123456caas.cn (J.W.)

[2 ]Ministry of Agriculture—Milk and Dairy Product Inspection Center (Beijing), Beijing 100193, China

[3 ]State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China

Author notes

[* ]Correspondence: zhengnan@ 123456caas.cn ; Tel.: +86-10-6281-6069

[†]

These authors contributed equally to this work.

Article

Publisher ID: ijms-17-01078

DOI: 10.3390/ijms17071078

PMC ID: 4964454

PubMed ID: 27447614

SO-VID: 501b61d6-3311-487e-86b4-2b2300c0d97f

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This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

Exploring the Molecular Basis for Binding of Inhibitors by Threonyl-tRNA Synthetase from Brucella abortus: A Virtual Screening Study

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Abstract

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Higher order chromatin architecture

Most cited references 42

CASTp: computed atlas of surface topography of proteins with structural and topographical mapping of functionally annotated residues

Protein structure prediction and structural genomics.

A method to identify protein sequences that fold into a known three-dimensional structure.

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