Where metal ions bind in proteins.

Yamashita, M M; Wesson, Laura; Eisenman, George; Eisenberg, David

doi:10.1073/pnas.87.15.5648

Cited by 306 publications

(265 citation statements)

References 27 publications

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“…The presence of positively charged residues close to the metalbinding site in the H4 tail can result in a siteselectivity association of the Ni(II) complexed tail with the negatively charged DNA backbone (41). In addition the hydrophobic environment in the entire protein is expected to enhance metal-binding capabilities because of multiple nonbonding interactions available there, as reported in the literature (42)(43)(44).…”

Section: Resultsmentioning

confidence: 75%

Molecular mechanisms in nickel carcinogenesis: modeling Ni(II) binding site in histone H4.

Zoroddu

Schinocca

Kowalik-Jankowska

et al. 2002

Environ Health Perspect

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Section: Resultsmentioning

confidence: 75%

Molecular mechanisms in nickel carcinogenesis: modeling Ni(II) binding site in histone H4.

Zoroddu

Schinocca

Kowalik-Jankowska

et al. 2002

Environ Health Perspect

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“…Typically, molecular interactions with diverse ligands occur on local surface regions of proteins, though the shape and size of the local regions vary in terms of ligand types: for example, a center in a shell of several hydrophilic protein residues for metal ions, 6 a concave-shaped structure (i.e., "pocket") for small molecules, and noncontiguous, relatively large, flat surfaces for proteins. 7 Therefore, local structure-centric characterization of proteins rather than global structures is needed to better understand biology.…”

Section: Introductionmentioning

confidence: 99%

G‐LoSA: An efficient computational tool for local structure‐centric biological studies and drug design

Lee

2016

Protein Science

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Molecular recognition by protein mostly occurs in a local region on the protein surface. Thus, an efficient computational method for accurate characterization of protein local structural conservation is necessary to better understand biology and drug design. We present a novel local structure alignment tool, G-LoSA. G-LoSA aligns protein local structures in a sequence order independent way and provides a GA-score, a chemical feature-based and size-independent structure similarity score. Our benchmark validation shows the robust performance of G-LoSA to the local structures of diverse sizes and characteristics, demonstrating its universal applicability to local structure-centric comparative biology studies. In particular, G-LoSA is highly effective in detecting conserved local regions on the entire surface of a given protein. In addition, the applications of GLoSA to identifying template ligands and predicting ligand and protein binding sites illustrate its strong potential for computer-aided drug design. We hope that G-LoSA can be a useful computational method for exploring interesting biological problems through large-scale comparison of protein local structures and facilitating drug discovery research and development. G-LoSA is freely available to academic users at http://im.compbio.ku.edu/GLoSA/.

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“…Factors that lead to a structural disruption of that context can result in a loss of selectivity of a binding site. Interestingly, a search through the structural database reveals that a common feature of ion-binding sites in proteins is the existence of a shell of nonpolar hydrophobic groups surrounding the ion-coordinating ligands (35). Presumably, this serves to provide a region of low dielectric to protect the confinement and enhance the local electrostatic interactions.…”

Section: Relative Freementioning

confidence: 99%

Two mechanisms of ion selectivity in protein binding sites

Noskov

Roux

2010

Proc. Natl. Acad. Sci. U.S.A.

165

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A theoretical framework is presented to clarify the molecular determinants of ion selectivity in protein binding sites. The relative free energy of a bound ion is expressed in terms of the main coordinating ligands coupled to an effective potential of mean force representing the influence of the rest of the protein. The latter is separated into two main contributions. The first includes all the forces keeping the ion and the coordinating ligands confined to a microscopic subvolume but does not prevent the ligands from adapting to a smaller or larger ion. The second regroups all the remaining forces that control the precise geometry of the coordinating ligands best adapted to a given ion. The theoretical framework makes it possible to delineate two important limiting cases. In the limit where the geometric forces are dominant (rigid binding site), ion selectivity is controlled by the ion-ligand interactions within the matching cavity size according to the familiar "snugfit" mechanism of host-guest chemistry. In the limit where the geometric forces are negligible, the ion and ligands behave as a "confined microdroplet" that is free to fluctuate and adapt to ions of different sizes. In this case, ion selectivity is set by the interplay between ion-ligand and ligand-ligand interactions and is controlled by the number and the chemical type of ion-coordinating ligands. The framework is illustrated by considering the ion-selective binding sites in the KcsA channel and the LeuT transporter.computations | free energy | ion coordination | KcsA | LeuT

show abstract

Where metal ions bind in proteins.

Cited by 306 publications

References 27 publications

Molecular mechanisms in nickel carcinogenesis: modeling Ni(II) binding site in histone H4.

Molecular mechanisms in nickel carcinogenesis: modeling Ni(II) binding site in histone H4.

G‐LoSA: An efficient computational tool for local structure‐centric biological studies and drug design

Two mechanisms of ion selectivity in protein binding sites

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