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Dive into the research topics where William H. Gmeiner is active.

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Featured researches published by William H. Gmeiner.


Journal of Biomolecular NMR | 1996

Improved 3D gd-HCACO and gd-(H)CACO-TOCSY experiments for isotopically enriched proteins dissolved in H2O

Weixing Zhang; William H. Gmeiner

SummaryPulsed field gradients were incorporated into the HCACO experiment for acquiring spectra on isotopically enriched protein samples dissolved in H2O. Excellent water suppression and spectral quality were achieved using the modified pulse sequence (gd-HCACO), as demonstrated for a 13C-/15N-labeled sample of the SH2 domain from the hematopoietic cellular kinase dissolved in 90% H2O/10% D2O. Strong correlations for all residues were observed in the gd-HCACO spectrum, even for residues having α-protons resonating exactly at the H2O frequency. The HCACO-TOCSY experiment was modified to correlate intraresidue 13Cα (rather than 1Hα), carbonyl (13C′), and aliphatic side-chain protons [(H)CACO-TOCSY]. Pulsed field gradients were also incorporated into the (H)CACO-TOCSY experiment for water suppression.


Journal of Biomolecular NMR | 1997

Three-dimensional structure of the Hck SH2 domain in solution

Weixing Zhang; Thomas E. Smithgall; William H. Gmeiner

The hematopoietic cellular kinase (Hck) is a member of the Srcfamily of non-receptor protein-tyrosine kinases that is expressedpredominantly in granulocytes, monocytes and macrophages. Recentobservations suggest that Hck may be activated in HIV-infected macrophagesand in chronic myelogenous leukemia cells that express Bcr-Abl. In order toincrease our understanding of the structural basis for regulation of Hckactivity under normal and pathological conditions, we have solved thesolution structure of the uncomplexed Hck SH2 domain using NMR spectroscopy.A novel procedure that uses intraresidueHN™Hα distances as references forconverting NOE intensities into distance restraints has been described. Atotal of 1757 significant experimental restraints were derived from NMRspectroscopic data including 238 medium-range and 487 long-range distancerestraints and 177 torsion angle restraints. These restraints were used in asimulated annealing procedure to generate 20 structures with the programDYANA. Superimposition of residues 5–104 upon the mean coordinate setyielded an average atomic rmsd values of 0.42 ± 0.08 Å for theN,Cα,C′ atoms and 0.81 ± 0.08 Å forall heavy atoms. Rmsd values for those residues in the regions of orderedsecondary structure were 0.27 ± 0.04 Å for theN,Cα,C′ atoms and 0.73 ± 0.06 Å forall heavy atoms.


FEBS Letters | 2000

Binding of ethidium to DNA measured using a 2D diffusion-modulated gradient COSY NMR experiment.

William H. Gmeiner; Christopher J. Hudalla; Ana Maria Soto; Luis A. Marky

The binding of ethidium bromide to a DNA hairpin (dU5‐hairpin) was investigated using a novel 2D diffusion‐modulated gradient correlation spectroscopy (DMG‐COSY) experiment to evaluate the applicability of this technique for studying the binding of drugs to DNA. The DMG‐COSY experiment includes a preparation period during which coherent magnetization is attenuated due to molecular self‐diffusion. Magnetization then evolves due to scalar coupling during an evolution delay, and is detected using gradient pulses for coherence selection. The time‐domain data are processed in an analogous manner as for gradient‐selected COSY experiments. The diffusion coefficient for uridine in DMSO solution was determined from the H5–H6 crosspeak intensities for a series of 2D DMG‐COSY experiments that differed in the magnitude of the gradient pulses applied during the preparation period of the DMG‐COSY experiment. The diffusion coefficient for uridine calculated from the DMG‐COSY experiments was identical (within experimental error) to that determined from 1D diffusion experiments (5.24×10−6 cm2/s at 26°C). The diffusion coefficients for ethidium bromide and for the dU5‐hairpin were first measured separately using the DMG‐COSY experiment, and then measured in the putative complex. The diffusion coefficient for free ethidium bromide (4.15×10−6 cm2/s at 26°C) was considerably larger than for the dU5‐hairpin (1.60×10−6 cm2/s at 26°C), as expected for the smaller molecule. The diffusion coefficient for ethidium was markedly decreased upon addition of the dU5‐hairpin, consistent with complex formation (1.22×10−6 cm2/s at 26°C). Complex formation of 1:1 stoichiometry between ethidium and the stem of the dU5‐hairpin was verified independently by fluorescence spectroscopy. These results demonstrate the utility of the DMG‐COSY experiment for investigating the binding of drugs to DNA in aqueous solution.


Journal of Biomolecular Structure & Dynamics | 1995

A linear 23-residue peptide reveals a propensity to form an unusual native-like conformation.

Simon A. Sherman; William H. Gmeiner; Leonid Kirnarskiy; Fulvio Perini; Raymond W. Ruddon

To gain insight into the earliest events of protein folding, a 23-residue peptide with a sequence corresponding to the 38-60 fragment of the beta-subunit of human chorionic gonadotropin (hCG beta) was studied by NMR. In aqueous solution the majority of the peptide residues adopted an extended polyproline II (PII) conformation similar to those in mature, fully folded hCG beta. The finding that the isolated protein fragment may acquire native-like structural motifs, even without alpha-helices or beta-structures, extends the possibility of using free peptides as model systems to better understand the protein folding mechanisms. It was shown that the PII-rich structural motif can be determined efficiently by NMR spectroscopy. The observation that in the absence of extensive medium- and long-range interactions the majority of amino acid residues may adopt the PII conformation suggests that the PII-rich structural motifs may play an important role in early events of protein folding.


FEBS Letters | 1997

Sequential assignment and secondary structure determination for the Src homology 2 domain of hematopoietic cellular kinase

Weixing Zhang; Thomas E. Smithgall; William H. Gmeiner

The hematopoietic cellular kinase (Hck) is a member of the Src family of non‐receptor protein–tyrosine kinases and participates in signal transduction events regulating the growth, differentiation and function of phagocytes. The secondary structure of the SH2 domain for Hck was determined for a 13C/15N‐enriched sample using multi‐dimensional NMR spectroscopy. The secondary structure for the domain was determined from chemical shift indices [1Hα, 13Cα and 13C′], sequential NOEs [d αN(i, i+1) and d NN(i, i+1)], and 3 J αN scalar coupling constants. The Hck SH2 domain consists of two α‐helices and seven β‐strands. Complementary strands of β‐sheets were identified from long‐range NOEs using a novel 3D, 13C/15N‐edited HMQC‐NOESY‐(HCACO)NH experiment that correlated 1Hα resonances between β‐strands. The secondary structure for Hck SH2 is similar to that predicted from the sequence alignment of the Src‐family protein tyrosine kinases.


Journal of Biomolecular NMR | 1996

A 3D NOESY-(HCACO)NH experiment for the measurement of NOEs involving 1H? in 13C-/15N-labeled proteins dissolved in H2O

Weixing Zhang; William H. Gmeiner

SummaryA 3D NOESY-(HCACO)NH experiment is described that transfers NOEs from 1Hα to the backbone 1HN in the succeeding residue for detection. Using this strategy, NOEs involving 1Hα protons that resonate exactly at the water frequency can be detected. NOEs from an overlapping 1Hα proton that is attached to degenerate 13Cα can also be resolved. The performance of this approach is demonstrated for the 13C-/15N-labeled Hck/SH2 dissolved in H2O.


Journal of Molecular Biology | 1999

Comparison of SH3 and SH2 domain dynamics when expressed alone or in an SH(3 + 2) construct: the role of protein dynamics in functional regulation

John R. Engen; Thomas E. Smithgall; William H. Gmeiner; David L. Smith


Journal of Molecular Biology | 1998

Solution structure of the human Hck SH3 domain and identification of its ligand binding site.

D. A. Horita; D. M. Baldisseri; Weixing Zhang; A. S. Altieri; Thomas E. Smithgall; William H. Gmeiner; R.A. Byrd


Protein Science | 2008

Dynamics of the Hck-SH3 domain: comparison of experiment with multiple molecular dynamics simulations.

David A. Horita; R. Andrew Byrd; Weixing Zhang; Thomas E. Smithgall; William H. Gmeiner


Journal of Biomolecular Structure & Dynamics | 1997

The 5′ Stem-Loop From Human U4 snRNA Adopts a Novel Conformation Stabilized by G-C and G-U Base Pairs

Parag V. Sahasrabudhe; Junqu Sun; William H. Gmeiner

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Thomas E. Smithgall

Eppley Institute for Research in Cancer and Allied Diseases

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Weixing Zhang

Eppley Institute for Research in Cancer and Allied Diseases

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David L. Smith

University of Nebraska–Lincoln

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R. Andrew Byrd

Food and Drug Administration

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Amanda S. Altieri

Science Applications International Corporation

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Ana Maria Soto

University of Nebraska Medical Center

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Christopher J. Hudalla

Eppley Institute for Research in Cancer and Allied Diseases

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