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Full-Text Articles in Physics

Characterization Of Pharmaceutical Cocrystals And Salts By Dynamic Nuclear Polarization-Enhanced Solid-State Nmr Spectroscopy, Li Zhao, Michael P. Hanrahan, Genetech, Inc., Aaron J. Rossini Feb 2018

Characterization Of Pharmaceutical Cocrystals And Salts By Dynamic Nuclear Polarization-Enhanced Solid-State Nmr Spectroscopy, Li Zhao, Michael P. Hanrahan, Genetech, Inc., Aaron J. Rossini

Ames Laboratory Accepted Manuscripts

Multicomponent solids such as cocrystals have emerged as a way to control and engineer the stability, solubility, and manufacturability of solid active pharmaceutical ingredients (APIs). Cocrystals are typically formed by solution- or solid-phase reactions of APIs with suitable cocrystal coformers, which are often weak acids. One key structural question about a given multicomponent solid is whether it should be classified as a salt, where the basic API is protonated by the acid, or as a cocrystal, where the API and coformer remain neutral and engage in hydrogen bonding interactions. It has previously been demonstrated that solid-state NMR spectroscopy is a ...


Morphological Transformations In The Magnetite Biomineralizing Protein Mms6 In Iron Solutions: A Small-Angle X‑Ray Scattering Study, Honghu Zhang, Xunpei Liu, Shuren Feng, Wenjie Wang, Klaus Schmidt-Rohr, Mufit Akinc, Marit Nilsen-Hamilton, David Vaknin, Surya K. Mallapragada Feb 2015

Morphological Transformations In The Magnetite Biomineralizing Protein Mms6 In Iron Solutions: A Small-Angle X‑Ray Scattering Study, Honghu Zhang, Xunpei Liu, Shuren Feng, Wenjie Wang, Klaus Schmidt-Rohr, Mufit Akinc, Marit Nilsen-Hamilton, David Vaknin, Surya K. Mallapragada

Chemical and Biological Engineering Publications

Magnetotactic bacteria that produce magnetic nanocrystals of uniform size and well-defined morphologies have inspired the use of biomineralization protein Mms6 to promote formation of uniform magnetic nanocrystals in vitro. Small angle X-ray scattering (SAXS) studies in physiological solutions reveal that Mms6 forms compact globular threedimensional (3D) micelles (approximately 10 nm in diameter) that are, to a large extent, independent of concentration. In the presence of iron ions in the solutions, the general micellar morphology is preserved, however, with associations among micelles that are induced by iron ions. Compared with Mms6, the m2Mms6 mutant (with the sequence of hydroxyl/carboxyl containing ...


Morphological Transformations In The Magnetite Biomineralizing Protein Mms6 In Iron Solutions: A Small-Angle X-Ray Scattering Study, Honghu Zhang, Xunpei Liu, Shuren Feng, Wenjie Wang, Klaus Schmidt-Rohr, Mufit Akinc, Marit Nilsen-Hamilton, David Vaknin, Surya K. Mallapragada Jan 2015

Morphological Transformations In The Magnetite Biomineralizing Protein Mms6 In Iron Solutions: A Small-Angle X-Ray Scattering Study, Honghu Zhang, Xunpei Liu, Shuren Feng, Wenjie Wang, Klaus Schmidt-Rohr, Mufit Akinc, Marit Nilsen-Hamilton, David Vaknin, Surya K. Mallapragada

Biochemistry, Biophysics and Molecular Biology Publications

Magnetotactic bacteria that produce magnetic nanocrystals of uniform size and well-defined morphologies have inspired the use of biomineralization protein Mms6 to promote formation of uniform magnetic nanocrystals in vitro. Small angle X-ray scattering (SAXS) studies in physiological solutions reveal that Mms6 forms compact globular three-dimensional (3D) micelles (approximately 10 nm in diameter) that are, to a large extent, independent of concentration. In the presence of iron ions in the solutions, the general micellar morphology is preserved, however, with associations among micelles that are induced by iron ions. Compared with Mms6, the m2Mms6 mutant (with the sequence of hydroxyl/carboxyl containing ...


Crystal Structure Of The Neisseria Gonorrhoeae Mtrd Inner Membrane Multidrug Efflux Pump, Jani Reddy Bolla, Chih-Chia Su, Sylvia V. Do, Pattathil Radhakrishnan, Nitin Kumar, Feng Long, Tsung-Han Chou, Jared A. Delmar, Hsiang-Ting Lei, Kanagalaghatta R. Rajashankar, William M. Shafer, Edward Yu Jan 2014

Crystal Structure Of The Neisseria Gonorrhoeae Mtrd Inner Membrane Multidrug Efflux Pump, Jani Reddy Bolla, Chih-Chia Su, Sylvia V. Do, Pattathil Radhakrishnan, Nitin Kumar, Feng Long, Tsung-Han Chou, Jared A. Delmar, Hsiang-Ting Lei, Kanagalaghatta R. Rajashankar, William M. Shafer, Edward Yu

Physics and Astronomy Publications

Neisseria gonorrhoeae is an obligate human pathogen and the causative agent of the sexually-transmitted disease gonorrhea. The control of this disease has been compromised by the increasing proportion of infections due to antibiotic-resistant strains, which are growing at an alarming rate. The MtrCDE tripartite multidrug efflux pump, belonging to the hydrophobic and amphiphilic efflux resistance-nodulation-cell division (HAE-RND) family, spans both the inner and outer membranes of N. gonorrhoeae and confers resistance to a variety of antibiotics and toxic compounds. We here report the crystal structure of the inner membrane MtrD multidrug efflux pump, which reveals a novel structural feature that ...


Crystal Structure Of The Open State Of The Neisseria Gonorrhoeae Mtre Outer Membrane Channel, Hsiang-Ting Lei, Tsung-Han Chou, Chih-Chia Su, Jani Reddy Bolla, Nitin Kumar, Pattathil Radhakrishnan, Feng Long, Jared A. Delmar, Sylvia V. Do, Kanagalaghatta R. Rajashankar, William M. Shafer, Edward Yu Jan 2014

Crystal Structure Of The Open State Of The Neisseria Gonorrhoeae Mtre Outer Membrane Channel, Hsiang-Ting Lei, Tsung-Han Chou, Chih-Chia Su, Jani Reddy Bolla, Nitin Kumar, Pattathil Radhakrishnan, Feng Long, Jared A. Delmar, Sylvia V. Do, Kanagalaghatta R. Rajashankar, William M. Shafer, Edward Yu

Physics and Astronomy Publications

Active efflux of antimicrobial agents is one of the most important strategies used by bacteria to defend against antimicrobial factors present in their environment. Mediating many cases of antibiotic resistance are transmembrane efflux pumps, composed of one or more proteins. The Neisseria gonorrhoeae MtrCDE tripartite multidrug efflux pump, belonging to the hydrophobic and amphiphilic efflux resistance-nodulation-cell division (HAE-RND) family, spans both the inner and outer membranes of N. gonorrhoeae and confers resistance to a variety of antibiotics and toxic compounds. We here describe the crystal structure of N. gonorrhoeae MtrE, the outer membrane component of the MtrCDE tripartite multidrug efflux ...


Structural And Functional Analysis Of The Transcriptional Regulator Rv3066 Of Mycobacterium Tuberculosis, Jani Reddy Bolla, Sylvia V. Do, Feng Long, Lei Dai, Chih-Chia Su, Hsiang-Ting Lei, Xiao Chen, Jillian E. Gerkey, Daniel C. Murphy, Kanagalaghatta R. Rajashankar, Qijing Zhang, Edward W. Yu Oct 2012

Structural And Functional Analysis Of The Transcriptional Regulator Rv3066 Of Mycobacterium Tuberculosis, Jani Reddy Bolla, Sylvia V. Do, Feng Long, Lei Dai, Chih-Chia Su, Hsiang-Ting Lei, Xiao Chen, Jillian E. Gerkey, Daniel C. Murphy, Kanagalaghatta R. Rajashankar, Qijing Zhang, Edward W. Yu

Veterinary Microbiology and Preventive Medicine Publications

The Mmr multidrug efflux pump recognizes and actively extrudes a broad range of antimicrobial agents, and promotes the intrinsic resistance to these antimicrobials in Mycobacterium tuberculosis . The expression of Mmr is controlled by the TetR-like transcriptional regulator Rv3066, whose open reading frame is located downstream of the mmr operon. To understand the structural basis of Rv3066 regulation, we have determined the crystal structures of Rv3066, both in the absence and presence of bound ethidium, revealing an asymmetric homodimeric two-domain molecule with an entirely helical architecture. The structures underscore the flexibility and plasticity of the regulator essential for multidrug recognition. Comparison ...


Interfacial Properties And Iron Binding To Bacterial Proteins That Promote The Growth Of Magnetite Nanocrystals: X-Ray Reflectivity And Surface Spectroscopy Studies, Wenjie Wang, Wei Bu, Lijun Wang, Pierre E. Palo, Surya K. Mallapragada, Marit Nilsen-Hamilton, David Vaknin Jan 2012

Interfacial Properties And Iron Binding To Bacterial Proteins That Promote The Growth Of Magnetite Nanocrystals: X-Ray Reflectivity And Surface Spectroscopy Studies, Wenjie Wang, Wei Bu, Lijun Wang, Pierre E. Palo, Surya K. Mallapragada, Marit Nilsen-Hamilton, David Vaknin

Biochemistry, Biophysics and Molecular Biology Publications

Surface sensitive X-ray scattering and spectroscopic studies have been conducted to determine structural properties of Mms6, the protein in Magnetospirillum magneticum AMB-1 that is implicated as promoter of magnetite nanocrystals growth. Surface pressure versus molecular area isotherms indicate Mms6 forms stable monolayers at the aqueous/vapor interface that are strongly affected by ionic conditions of the subphase. Analysis of X-ray reflectivity from the monolayers shows that the protein conformation at the interface depends on surface pressure and on the presence of ions in the solutions, in particular of iron ions and its complexes. X-ray fluorescence at grazing angles of incidence ...


Self-Assembly And Biphasic Iron-Binding Characteristics Of Mms6, A Bacterial Protein That Promotes The Formation Of Superparamagnetic Magnetite Nanoparticles Of Uniform Size And Shape, Lijun Wang, Tanya Prozorov, Pierre E. Palo, Xunpei Liu, David Vaknin, Ruslan Prozorov, Surya K. Mallapragada, Marit Nilsen-Hamilton Jan 2012

Self-Assembly And Biphasic Iron-Binding Characteristics Of Mms6, A Bacterial Protein That Promotes The Formation Of Superparamagnetic Magnetite Nanoparticles Of Uniform Size And Shape, Lijun Wang, Tanya Prozorov, Pierre E. Palo, Xunpei Liu, David Vaknin, Ruslan Prozorov, Surya K. Mallapragada, Marit Nilsen-Hamilton

Biochemistry, Biophysics and Molecular Biology Publications

Highly ordered mineralized structures created by living organisms are often hierarchical in structure with fundamental structural elements at nanometer scales. Proteins have been found responsible for forming many of these structures, but the mechanisms by which these biomineralization proteins function are generally poorly understood. To better understand its role in biomineralization, the magnetotactic bacterial protein, Mms6, which promotes the formation in vitro of superparamagnetic magnetite nanoparticles of uniform size and shape, was studied for its structure and function. Mms6 is shown to have two phases of iron binding: one high affinity and stoichiometric and the other low affinity, high capacity ...


Crystal Structure Of The Cusba Heavy-Metal Efflux Complex Of Escherichia Coli, Chih-Chia Su, Feng Long, Michael T. Zimmermann, Kanagalaghatta R. Rajashankar, Robert L. Jernigan, Edward W. Yu Jan 2011

Crystal Structure Of The Cusba Heavy-Metal Efflux Complex Of Escherichia Coli, Chih-Chia Su, Feng Long, Michael T. Zimmermann, Kanagalaghatta R. Rajashankar, Robert L. Jernigan, Edward W. Yu

Biochemistry, Biophysics and Molecular Biology Publications

Gram-negative bacteria, such as Escherichia coli, expel toxic chemicals via tripartite efflux pumps spanning both the inner and outer membranes. The three parts are: 1) a membrane fusion protein connecting 2) a substrate-binding inner membrane transporter to 3) an outer membrane-anchored channel in the periplasmic space. A crystallographic model of this tripartite efflux complex has been unavailable simply because co-crystallization of different components of the system has proven to be extremely difficult. We previously described the crystal structures of both the inner membrane transporter CusA1 and membrane fusion protein CusB2 of the CusCBA efflux system3,4 from ...


Destabilization Of Ag Nanoislands On Ag(100) By Adsorbed Sulfur, Mingmin Shen, Selena M. Russell, Da-Jiang Liu, Patricia A. Thiel Jan 2011

Destabilization Of Ag Nanoislands On Ag(100) By Adsorbed Sulfur, Mingmin Shen, Selena M. Russell, Da-Jiang Liu, Patricia A. Thiel

Chemistry Publications

Sulfur accelerates coarsening of Ag nanoislands on Ag(100) at 300 K, and this effect is enhanced with increasing sulfur coverage over a range spanning a few hundredths of a monolayer, to nearly 0.25 monolayers. We propose that acceleration of coarsening in this system is tied to the formation of AgS2 clusters primarily at step edges. These clusters can transport Ag more efficiently than can Ag adatoms (due to a lower diffusion barrier and comparable formation energy). The mobility of isolated sulfur on Ag(100) is very low so that formation of the complex is kinetically limited at ...


Crystal Structures Of The Cusa Efflux Pump Suggest Methionine-Mediated Metal Transport, Feng Long, Chih-Chia Su, Michael T. Zimmermann, Scott E. Boyken, Kanagalaghatta R. Rajashankar, Robert L. Jernigan, Edward W. Yu Jan 2010

Crystal Structures Of The Cusa Efflux Pump Suggest Methionine-Mediated Metal Transport, Feng Long, Chih-Chia Su, Michael T. Zimmermann, Scott E. Boyken, Kanagalaghatta R. Rajashankar, Robert L. Jernigan, Edward W. Yu

Biochemistry, Biophysics and Molecular Biology Publications

Gram-negative bacteria, such as Escherichia coli, frequently utilize tripartite efflux complexes in the resistance-nodulation-cell division (RND) family to expel diverse toxic compounds from the cell.1,2 The efflux system CusCBA is responsible for extruding biocidal Cu(I) and Ag(I) ions.3,4 No prior structural information was available for the heavy-metal efflux (HME) subfamily of the RND efflux pumps. Here we describe the crystal structures of the inner membrane transporter CusA in the absence and presence of bound Cu(I) or Ag(I). These CusA structures provide important new structural information about the HME sub-family of RND efflux ...


Electrostatic Correlations At The Stern Layer: Physics Or Chemistry?, Alex Travesset Jan 2009

Electrostatic Correlations At The Stern Layer: Physics Or Chemistry?, Alex Travesset

Physics and Astronomy Publications

We introduce a minimal free energy describing the interaction of charged groups and counterions including both classical electrostatic and specific interactions. The predictions of the model are compared against the standard model for describing ions next to charged interfaces, consisting of Poisson–Boltzmann theory with additional constants describing ion binding, which are specific to the counterion and the interfacial charge (“chemical binding”). It is shown that the “chemical” model can be appropriately described by an underlying “physical” model over several decades in concentration, but the extracted binding constants are not uniquely defined, as they differ depending on the particular observable ...


Structural Model Of The Rev Regulatory Protein From Equine Infectious Anemia Virus, Yungok Ihm, Wendy O. Sparks, Jae-Hyung Lee, Haibo Cao, Susan Carpenter, Cai-Zhuang Wang, Kai-Ming Ho, Drena Dobbs Jan 2009

Structural Model Of The Rev Regulatory Protein From Equine Infectious Anemia Virus, Yungok Ihm, Wendy O. Sparks, Jae-Hyung Lee, Haibo Cao, Susan Carpenter, Cai-Zhuang Wang, Kai-Ming Ho, Drena Dobbs

Genetics, Development and Cell Biology Publications

Rev is an essential regulatory protein in the equine infectious anemia virus (EIAV) and other lentiviruses, including HIV-1. It binds incompletely spliced viral mRNAs and shuttles them from the nucleus to the cytoplasm, a critical prerequisite for the production of viral structural proteins and genomic RNA. Despite its important role in production of infectious virus, the development of antiviral therapies directed against Rev has been hampered by the lack of an experimentally-determined structure of the full length protein. We have used a combined computational and biochemical approach to generate and evaluate a structural model of the Rev protein. The modeled ...


Conformational Change Of The Acrr Regulator Reveals A Possible Mechanism Of Induction, Ruoyu Gu, Ming Li, Chih-Chia Su, Feng Long, Matthew D. Routh, Feng Yang, Gerry Mcdermott, Edward Yu Jan 2008

Conformational Change Of The Acrr Regulator Reveals A Possible Mechanism Of Induction, Ruoyu Gu, Ming Li, Chih-Chia Su, Feng Long, Matthew D. Routh, Feng Yang, Gerry Mcdermott, Edward Yu

Physics and Astronomy Publications

The Escherichia coli AcrR multidrug-binding protein represses transcription of acrAB and is induced by many structurally unrelated cytotoxic compounds. The crystal structure of AcrR in space group P2221 has been reported previously. This P2221 structure has provided direct information about the multidrug-binding site and important residues for drug recognition. Here, a crystal structure of this regulator in space group P31 is presented. Comparison of the two AcrR structures reveals possible mechanisms of ligand binding and AcrR regulation.


Crystallization And Preliminary X-Ray Diffraction Analysis Of The Multidrug Efflux Transporter Norm From Neisseria Gonorrhoeae, Chih-Chia Su, Feng Long, Gerry Mcdermott, William M. Shafer, Edward Yu Jan 2008

Crystallization And Preliminary X-Ray Diffraction Analysis Of The Multidrug Efflux Transporter Norm From Neisseria Gonorrhoeae, Chih-Chia Su, Feng Long, Gerry Mcdermott, William M. Shafer, Edward Yu

Physics and Astronomy Publications

The crystallization and preliminary X-ray data analysis of the NorM multidrug efflux pump produced by Neisseria gonorrhoeae are reported. NorM is a cytoplasmic membrane protein that consists of 459 amino-acid residues. It is a member of the recently classified multidrug and toxic compound extrusion (MATE) family of transporters and recognizes a number of cationic toxic compounds such as ethidium bromide, acriflavin, 2-N-methylellipticinium and ciprofloxacin. Recombinant NorM protein was expressed in Escherichia coli and purified by metal-affinity and gel-filtration chromatography. The protein was crystallized using hanging-drop vapor diffusion. X-ray diffraction data were collected from cryocooled crystals at a synchrotron ...


Conformation Of The Acrb Multidrug Efflux Pump In Mutants Of The Putative Proton Relay Pathway, Chih-Chia Su, Ming Li, Ruoyu Gu, Yumiko Takatsuka, Gerry Mcdermott, Hiroshi Nikaido, Edward Yu Jan 2006

Conformation Of The Acrb Multidrug Efflux Pump In Mutants Of The Putative Proton Relay Pathway, Chih-Chia Su, Ming Li, Ruoyu Gu, Yumiko Takatsuka, Gerry Mcdermott, Hiroshi Nikaido, Edward Yu

Physics and Astronomy Publications

We previously reported the X-ray structures of wild-type Escherichia coli AcrB, a proton motive force-dependent multidrug efflux pump, and its N109A mutant. These structures presumably reflect the resting state of AcrB, which can bind drugs. After ligand binding, a proton may bind to an acidic residue(s) in the transmembrane domain, i.e., Asp407 or Asp408, within the putative network of electrostatically interacting residues, which also include Lys940 and Thr978, and this may initiate a series of conformational changes that result in drug expulsion. Herein we report the X-ray structures of four AcrB mutants, the D407A, D408A, K940A, and T978A ...


Predicting Binding Sites Of Hydrolase-Inhibitor Complexes By Combining Several Methods, Taner Z. Sen, Andrzej Kloczkowski, Robert L. Jernigan, Changhui Yan, Vasant Honovar, Kai-Ming Ho, Cai-Zhuang Wang, Yungok Ihm, Haibo Cao, Xun Gu, Drena Dobbs Jan 2004

Predicting Binding Sites Of Hydrolase-Inhibitor Complexes By Combining Several Methods, Taner Z. Sen, Andrzej Kloczkowski, Robert L. Jernigan, Changhui Yan, Vasant Honovar, Kai-Ming Ho, Cai-Zhuang Wang, Yungok Ihm, Haibo Cao, Xun Gu, Drena Dobbs

Genetics, Development and Cell Biology Publications

Background

Protein-protein interactions play a critical role in protein function. Completion of many genomes is being followed rapidly by major efforts to identify interacting protein pairs experimentally in order to decipher the networks of interacting, coordinated-in-action proteins. Identification of protein-protein interaction sites and detection of specific amino acids that contribute to the specificity and the strength of protein interactions is an important problem with broad applications ranging from rational drug design to the analysis of metabolic and signal transduction networks.

Results

In order to increase the power of predictive methods for protein-protein interaction sites, we have developed a consensus methodology ...