Journal of Structural and Functional Genomics

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Crystal structure of a macrophage migration inhibitory factor from Giardia lamblia.

Publication Date: 2013 May 25 PMID: 23709284
Authors: Buchko, G. W. - Abendroth, J. - Robinson, H. - Zhang, Y. - Hewitt, S. N. - Edwards, T. E. - Van Voorhis, W. C. - Myler, P. J.
Journal: J Struct Funct Genomics

Macrophage migration inhibitory factor (MIF) is a eukaryotic cytokine that affects a broad spectrum of immune responses and its activation/inactivation is associated with numerous diseases. During protozoan infections MIF is not only expressed by the host, but, has also been observed to be expressed by some parasites and released into the host. To better understand the biological role of parasitic MIF proteins, the crystal structure of the MIF protein from Giardia lamblia (Gl-MIF), the etiological agent responsible for giardiasis, has been determined at 2.30 A resolution. The 114-residue protein adopts an alpha/beta fold consisting of a four-stranded beta-sheet with two anti-parallel alpha-helices packed against a face of the beta-sheet. An additional short beta-strand aligns anti-parallel to beta4 of the beta-sheet in the adjacent protein unit to help stabilize a trimer, the biologically relevant unit observed in all solved MIF crystal structures to date, and form a discontinuous beta-barrel. The structure of Gl-MIF is compared to the MIF structures from humans (Hs-MIF) and three Plasmodium species (falciparum, berghei, and yoelii). The structure of all five MIF proteins are generally similar with the exception of a channel that runs through the center of each trimer complex. Relative to Hs-MIF, there are differences in solvent accessibility and electrostatic potential distribution in the channel of Gl-MIF and the Plasmodium-MIFs due primarily to two "gate-keeper" residues in the parasitic MIFs. For the Plasmodium MIFs the gate-keeper residues are at positions 44 (Y-->R) and 100 (V-->D) and for Gl-MIF it is at position 100 (V-->R). If these gate-keeper residues have a biological function and contribute to the progression of parasitemia they may also form the basis for structure-based drug design targeting parasitic MIF proteins.

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Crystal structure of AcrB complexed with linezolid at 3.5 A resolution.

Publication Date: 2013 May 15 PMID: 23673416
Authors: Hung, L. W. - Kim, H. B. - Murakami, S. - Gupta, G. - Kim, C. Y. - Terwilliger, T. C.
Journal: J Struct Funct Genomics

AcrB is an inner membrane resistance-nodulation-cell division efflux pump and is part of the AcrAB-TolC tripartite efflux system. We have determined the crystal structure of AcrB with bound Linezolid at a resolution of 3.5 A. The structure shows that Linezolid binds to the A385/F386 loops of the symmetric trimer of AcrB. A conformational change of a loop in the bottom of the periplasmic cleft is also observed.

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Computational identification and analysis of arsenate reductase protein in Cronobacter sakazakii ATCC BAA-894 suggests potential microorganism for reducing arsenate.

Publication Date: 2013 May 12 PMID: 23666632
Authors: Chaturvedi, N. - Singh, V. K. - Pandey, P. N.
Journal: J Struct Funct Genomics

This study focuses a bioinformatics-based prediction of arsC gene product arsenate reductase (ArsC) protein in Cronobacter sakazakii BAA-894 strain. A protein structure-based study encloses three-dimensional structural modeling of target ArsC protein, was carried out by homology modeling method. Ultimately, the detection of active binding regions was carried out for characterization of functional sites in protein. The ten probable ligand binding sites were predicted for target protein structure and highlighted the common binding residues between target and template protein. It has been first time identified that modeled ArsC protein structure in C. sakazakii was structurally and functionally similar to well-characterized ArsC protein of Escherichia coli because of having same structural motifs and fold with similar protein topology and function. Investigation revealed that ArsC from C. sakazakii can play significant role during arsenic resistance and potential microorganism for bioremediation of arsenic toxicity.

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Crystal structure of human Karyopherin beta2 bound to the PY-NLS of Saccharomyces cerevisiae Nab2.

Publication Date: 2013 Mar 28 PMID: 23535894
Authors: Soniat, M. - Sampathkumar, P. - Collett, G. - Gizzi, A. S. - Banu, R. N. - Bhosle, R. C. - Chamala, S. - Chowdhury, S. - Fiser, A. - Glenn, A. S. - Hammonds, J. - Hillerich, B. - Khafizov, K. - Love, J. D. - Matikainen, B. - Seidel, R. D. - Toro, R. - Rajesh Kumar, P. - Bonanno, J. B. - Chook, Y. M. - Almo, S. C.
Journal: J Struct Funct Genomics

Import-Karyopherin or Importin proteins bind nuclear localization signals (NLSs) to mediate the import of proteins into the cell nucleus. Karyopherin beta2 or Kapbeta2, also known as Transportin, is a member of this transporter family responsible for the import of numerous RNA binding proteins. Kapbeta2 recognizes a targeting signal termed the PY-NLS that lies within its cargos to target them through the nuclear pore complex. The recognition of PY-NLS by Kapbeta2 is conserved throughout eukaryotes. Kap104, the Kapbeta2 homolog in Saccharomyces cerevisiae, recognizes PY-NLSs in cargos Nab2, Hrp1, and Tfg2. We have determined the crystal structure of Kapbeta2 bound to the PY-NLS of the mRNA processing protein Nab2 at 3.05-A resolution. A seven-residue segment of the PY-NLS of Nab2 is observed to bind Kapbeta2 in an extended conformation and occupies the same PY-NLS binding site observed in other Kapbeta2.PY-NLS structures.

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