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Articles 1 - 11 of 11

Full-Text Articles in Medicinal-Pharmaceutical Chemistry

Crystal Structure Of The Alcanivorax Borkumensis Ydah Transporter Reveals An Unusual Topology, Jani Reddy Bolla, Chih-Chia Su, Jared A. Delmar, Pattathil Radhakrishnan, Nitin Kumar, Tsung-Han Chou, Feng Long, Kanagalaghatta R. Rajashankar, Edward Yu Jan 2015

Crystal Structure Of The Alcanivorax Borkumensis Ydah Transporter Reveals An Unusual Topology, Jani Reddy Bolla, Chih-Chia Su, Jared A. Delmar, Pattathil Radhakrishnan, Nitin Kumar, Tsung-Han Chou, Feng Long, Kanagalaghatta R. Rajashankar, Edward Yu

Physics and Astronomy Publications

The potential of the folic acid biosynthesis pathway as a target for the development of antibiotics has been clinically validated. However, many pathogens have developed resistance to these antibiotics, prompting a re-evaluation of potential drug targets within the pathway. The ydaH gene of Alcanivorax borkumensis encodes an integral membrane protein of the AbgT family of transporters for which no structural information was available. Here we report the crystal structure of A. borkumensis YdaH, revealing a dimeric molecule with an architecture distinct from other families of transporters. YdaH is a bowl-shaped dimer with a solvent-filled basin extending from the cytoplasm to ...


Structure And Function Of Neisseria Gonorrhoeae Mtrf Illuminates A Class Of Antimetabolite Efflux Pumps, Chih-Chia Su, Jani Reddy Bolla, Nitin Kumar, Pattathil Radhakrishnan, Feng Long, Jared A. Delmar, Tsung-Han Chou, Kanagalaghatta R. Rajashankar, William M. Shafer, Edward Yu Jan 2015

Structure And Function Of Neisseria Gonorrhoeae Mtrf Illuminates A Class Of Antimetabolite Efflux Pumps, Chih-Chia Su, Jani Reddy Bolla, Nitin Kumar, Pattathil Radhakrishnan, Feng Long, Jared A. Delmar, Tsung-Han Chou, 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. N. gonorrhoeae MtrF is an integral membrane protein that belongs to the AbgT family of transporters for which no structural information is available. Here, we describe the crystal structure of MtrF, revealing a dimeric molecule with architecture distinct from all other families of transporters. MtrF is a bowl-shaped dimer with a solvent-filled basin extending from the cytoplasm to ...


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 ...


Functional Cloning And Characterization Of The Multidrug Efflux Pumps Norm From Neisseria Gonorrhoeae And Ydhe From Escherichia Coli, Feng Long, Corrinne Rouquette-Loughlin, William M. Shafer, Edward Yu Jan 2008

Functional Cloning And Characterization Of The Multidrug Efflux Pumps Norm From Neisseria Gonorrhoeae And Ydhe From Escherichia Coli, Feng Long, Corrinne Rouquette-Loughlin, William M. Shafer, Edward Yu

Physics and Astronomy Publications

Active efflux of antimicrobial agents is one of the most important adapted strategies that bacteria use to defend against antimicrobial factors that are present in their environment. The NorM protein of Neisseria gonorrhoeae and the YdhE protein of Escherichia coli have been proposed to be multidrug efflux pumps that belong to the multidrug and toxic compound extrusion (MATE) family. In order to determine their antimicrobial export capabilities, we cloned, expressed, and purified these two efflux proteins and characterized their functions both in vivo and in vitro. E. coli strains expressing norM or ydhE showed elevated (twofold or greater) resistance to ...


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 ...


Preliminary Structural Studies Of The Transcriptional Regulator Cmer From Campylobacter Jejuni, Chih-Chia Su, Feng Shi, Ruoyu Gu, Ming Li, Gerry Mcdermott, Edward Yu, Qijing Zhang Jan 2007

Preliminary Structural Studies Of The Transcriptional Regulator Cmer From Campylobacter Jejuni, Chih-Chia Su, Feng Shi, Ruoyu Gu, Ming Li, Gerry Mcdermott, Edward Yu, Qijing Zhang

Physics and Astronomy Publications

In Campylobacter jejuni, a Gram-negative bacterial pathogen causing gastroenteritis in humans, the CmeR regulatory protein controls transcription of the multidrug transporter gene operon cmeABC. CmeR belongs to the TetR family of transcriptional regulators. The 210-residue CmeR consists of two functional motifs: an N-terminal DNA-binding domain and a C-terminal ligand-binding domain. It is predicted that the DNA-binding domain interacts directly with target promoters, while the C-terminal motif interacts with inducing ligands (such as bile salts). As an initial step towards confirming this structural model, recombinant CmeR protein containing a 6×His tag at the N-terminus was crystallized. Crystals of ligand-free CmeR ...


Cloning, Expression, Purification, Crystallization And Preliminary X-Ray Diffraction Analysis Of The Regulator Acrr From Escherichia Coli, Ming Li, Xi Qiu, Chih-Chia Su, Feng Long, Ruoyu Gu, Gerry Mcdermott, Edward Yu Jan 2006

Cloning, Expression, Purification, Crystallization And Preliminary X-Ray Diffraction Analysis Of The Regulator Acrr From Escherichia Coli, Ming Li, Xi Qiu, Chih-Chia Su, Feng Long, Ruoyu Gu, Gerry Mcdermott, Edward Yu

Physics and Astronomy Publications

This paper describes the cloning, expression, purification and preliminary X-ray data analysis of the AcrR regulatory protein. The Escherichia coli AcrR is a member of the TetR family of transcriptional regulators. It regulates the expression of the AcrAB multidrug transporter. Recombinant AcrR with a 6×His tag at the C-terminus was expressed in E. coli and purified by metal-affinity chromatography. The protein was crystallized using hanging-drop vapor diffusion. X-ray diffraction data were collected from cryocooled crystals at a synchrotron light source. The best crystal diffracted to 2.5 Å. The space group was determined to be P32, with ...


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 ...


A Periplasmic Drug-Binding Site Of The Acrb Multidrug Efflux Pump: A Crystallographic And Site-Directed Mutagenesis Study, Edward Yu, Juilo R. Aires, Gerry Mcdermott, Hiroshi Nikaido Jan 2005

A Periplasmic Drug-Binding Site Of The Acrb Multidrug Efflux Pump: A Crystallographic And Site-Directed Mutagenesis Study, Edward Yu, Juilo R. Aires, Gerry Mcdermott, Hiroshi Nikaido

Physics and Astronomy Publications

The Escherichia coli AcrB multidrug efflux pump is a membrane protein that recognizes many structurally dissimilar toxic compounds. We previously reported the X-ray structures of four AcrB-ligand complexes in which the ligands were bound to the wall of the extremely large central cavity in the transmembrane domain of the pump. Genetic studies, however, suggested that discrimination between the substrates occurs mainly in the periplasmic domain rather than the transmembrane domain of the pump. We here describe the crystal structures of the AcrB mutant in which Asn109 was replaced by Ala, with five structurally diverse ligands, ethidium, rhodamine 6G, ciprofloxacin, nafcillin ...