The unique hydrogen bonded water in the reduced form of Clostridium pasteurianum rubredoxin and its possible role in electron transfer

Park, Il Yeong; Youn, BuHyun; Harley, J.L.; Eidsness, Marly K.; Smith, Eugene T.; Ichiye, Toshiko; Kang, ChulHee

doi:10.1007/s00775-004-0542-3

Cited by 19 publications

(28 citation statements)

References 17 publications

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“…Our method could detect such similar regions irrespective of the arrangement of secondary structures or fold topologies. As well as this salient example, we observed large numbers of other pairs of metal ion‐binding sites shared across distinct proteins, such as similar iron (+2) cation (Fe 2+ ) binding sites between ribonucleotide‐triphosphate reductase (PDB ID: 1H7A)59 and rubredoxin (PDB ID: 1SMU)60 and similar manganese (+2) cation (Mn 2+ ) binding sites between glutamine synthetase (PDB ID: 1LGR)61 and mRNA triphosphatase (PDB ID: 1D8H) 62. We also observed a number of similar binding sites with metal substitutions, such as (Zn 2+ , Cd 2+ ), (Zn 2+ , Fe 2+ ), (Mg 2+ , Ca 2+ ), and (Mn 2+ , Fe 2+ ).…”

Section: Resultsmentioning

confidence: 72%

PDB‐scale analysis of known and putative ligand‐binding sites with structural sketches

et al. 2011

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Computational investigation of protein functions is one of the most urgent and demanding tasks in the field of structural bioinformatics. Exhaustive pairwise comparison of known and putative ligand-binding sites, across protein families and folds, is essential in elucidating the biological functions and evolutionary relationships of proteins. Given the vast amounts of data available now, existing 3D structural comparison methods are not adequate due to their computation time complexity. In this article, we propose a new bit string representation of binding sites called structural sketches, which is obtained by random projections of triplet descriptors. It allows us to use ultra-fast all-pair similarity search methods for strings with strictly controlled error rates. Exhaustive comparison of 1.2 million known and putative binding sites finished in ∼30 h on a single core to yield 88 million similar binding site pairs. Careful investigation of 3.5 million pairs verified by TM-align revealed several notable analogous sites across distinct protein families or folds. In particular, we succeeded in finding highly plausible functions of several pockets via strong structural analogies. These results indicate that our method is a promising tool for functional annotation of binding sites derived from structural genomics projects.

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Section: Resultsmentioning

confidence: 72%

PDB‐scale analysis of known and putative ligand‐binding sites with structural sketches

et al. 2011

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“…16,[29][30][31][32][33] We distinguish three types of H-bonds ( Figure 1a) (HB1, HB2, HB3, depicted in Scheme 1). Each of the ISC sulfur atoms, S1 and S3, is engaged in two H-bonds, which we call type HB1 and HB2.…”

Section: Isc H-bonds In Rdmentioning

confidence: 99%

Understanding Rubredoxin Redox Potentials: Role of H-Bonds on Model Complexes

Gámiz‐Hernández

Galstyan

Knapp

2009

J. Chem. Theory Comput.

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The energetics of redox states in different models of rubredoxin-like iron-sulfur complexes (ISC) was computed using a combination of density functional and electrostatic continuum theories. In agreement with experiment, the calculated redox potential for the small ISC model [Fe(SCH2CH3)4](1-,2-) in acetonitrile was -813 mV [Galstyan, A. S.; Knapp, E. W. J. Comput. Chem. 2009, 30, 203-211] as compared to the measured value of -838 mV. Surprisingly the experimental values for rubredoxin (Rd) are much higher ranging between -87 and +39 mV. These large variations in redox potentials of ISC models and ISC in Rd are due to specific conformational symmetries adopted by the ligands due to both the protein environment and type and the number of H-bonds, and the dielectric environment. In a dielectric environment corresponding to proteins (ε = 20), the computed ISC redox potentials shift positive by about 64 mV for Fe-S···H-N and 95 mV for Fe-S···H-O H-bonds, correlating well with data estimated from experiments on ISC proteins. In aqueous solutions (ε = 80), a positive shift of 58 mV was computed for Fe-S···H-O H-bonds (using a model with the same ISC conformation as in Rd) in agreement with a measured value for Rd with partially solvent exposed ISC. The latter demonstrates the dependence of the ISC redox potentials on the environment (solvent or protein). For a model whose chemical composition is analog to the relevant part of ISC in a specific Rd, the computed redox potential of the model agrees with the measured value in Rd. This study allows to understand redox potential shifts for small ISC models and ISC in proteins.

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“…Therefore, assessing the relative accuracy is important, as many researchers do not have access to computational resources for multi-nanosecond scale MD simulations for simple screening of potential mutants. In computational studies of rubredoxins (12), which have been experimentally verified (13,15,27), and ferredoxins (28), which have also been experimentally verified (29)(30)(31), sequence determinants involve changes in distance of <0.5 Å of polar groups hydrogen-bonded to the cluster and changes in energy of 50-100 meV. In particular, sequence determinant(s) of changes between homologous proteins can be difficult to identify as they may involve small changes mixed with many other irrelevant changes.…”

Section: Introductionmentioning

confidence: 94%

“…Furthermore, residue 44 has been identified as a sequence determinant of the reduction potential in rubredoxins, so a larger nonpolar Val side chain at residue 44 results in lower reduction potentials by~50 mV relative to a smaller Ala side chain because of a backbone shift (12)(13)(14). The third possible determinant is Ala 176 , which is equivalent to Leu 41 in CpRd, where it acts as a water gate (15)(16)(17). The smaller Ala might increase the reduction potential by exposing the redox site more to solvent, which would increase the reduction potential.…”

Section: Introductionmentioning

confidence: 99%

“…Here, we examine the linearity of the response of specific residues rather than the entire protein in comparisons of x-ray structures of homologous proteins and multi-nanosecond MD simulations of mutants. The work presented here utilizes methods developed earlier (12)(13)(14)(15) to elucidate the individual contributions of these possible determinants to the increased reduction potential of the rubredoxin domain of rubrerythrin over that of rubredoxin from analysis of crystal structure of wild-type (wt) DvRr and CpRd, as well as MD simulations of wt and mutant rubredoxins. Specifically, the aim is to examine the effects of mutation to asparagine, histidine, and alanine as found in DvRr in the equivalent positions of CpRd, and to relate these results to differences between DvRr and CpRd in their experimental reduction potentials.…”

Section: Introductionmentioning

confidence: 99%

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The Molecular Determinants of the Increased Reduction Potential of the Rubredoxin Domain of Rubrerythrin Relative to Rubredoxin

Luo

Ergenekan

Tan

et al. 2010

Biophysical Journal

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Based on the crystal structures, three possible sequence determinants have been suggested as the cause of a 285 mV increase in reduction potential of the rubredoxin domain of rubrerythrin over rubredoxin by modulating the polar environment around the redox site. Here, electrostatic calculations of crystal structures of rubredoxin and rubrerythrin and molecular dynamics simulations of rubredoxin wild-type and mutants are used to elucidate the contributions to the increased reduction potential. Asn(160) and His(179) in rubrerythrin versus valines in rubredoxins are predicted to be the major contributors, as the polar side chains contribute significantly to the electrostatic potential in the redox site region. The mutant simulations show both side chains rotating on a nanosecond timescale between two conformations with different electrostatic contributions. Reduction also causes a change in the reduction energy that is consistent with a linear response due to the interesting mechanism of shifting the relative populations of the two conformations. In addition to this, a simulation of a triple mutant indicates the side-chain rotations are approximately anticorrelated so whereas one is in the high potential conformation, the other is in the low potential conformation. However, Ala(176) in rubrerythrin versus a leucine in rubredoxin is not predicted to be a large contributor, because the solvent accessibility increases only slightly in mutant simulations and because it is buried in the interface of the rubrerythrin homodimer.

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The unique hydrogen bonded water in the reduced form of Clostridium pasteurianum rubredoxin and its possible role in electron transfer

Cited by 19 publications

References 17 publications

PDB‐scale analysis of known and putative ligand‐binding sites with structural sketches

PDB‐scale analysis of known and putative ligand‐binding sites with structural sketches

Understanding Rubredoxin Redox Potentials: Role of H-Bonds on Model Complexes

The Molecular Determinants of the Increased Reduction Potential of the Rubredoxin Domain of Rubrerythrin Relative to Rubredoxin

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