Beis, Konstantinos - Imperial College London - Department of Life Sciences, Biochemistry and Biotechnology

个人简介

MEMBRANE PROTEIN CRYSTALLOGRAPHY Membrane proteins represent around 30% of the proteomes of most organisms and more than 40% of drug targets and yet few structures of these molecules have been solved by x-ray crystallography. Drug resistance of bacterial pathogens is a rising crisis. Bacterial membrane proteins are essential for resistance since they are involved in the export of the drugs from the cell. My group is interested in the structural and functional characterisation of multidrug membrane transporters by X-ray crystallography. We are also interested to exploit novel antibacterials as treatments for bacterial infections. Bacteria under nutrient starvation can produce antibacterial peptides that hijack outer and inner membrane proteins for internalisation and cell death. These peptides are also toxic to the producing bacteria which utilise ABC-transporters to provide them with immunity. We have solved the structure and fully characterised the ABC-transporter McjD. The protein is in an outward-occluded state and provides key mechanistic information on this family of transporters. We also solved the Crystal structure of FhuA (blue and gold) in complex with MccJ25 (pink).structure of the outer membrane FhuA in complex with the antibacterial peptide MccJ25. The structure explains how antibacterial peptides can hijack the outer membrane and be internalised.

研究领域

My group is interested in the structure elucidation of membrane proteins involved in drug transport. In addition, we are looking to understand how the bacterial cells can sense and respond to antibiotics at the DNA level. We are also interested to understand how bacteria detoxify heavy metals by using enzymes and membrane proteins.

近期论文

查看导师最新文章（温馨提示：请注意重名现象，建议点开原文通过作者单位确认）

Mehmood S, Corradi V, Choudhury HG, Hussain R, Becker P, Axford D, Zirah S, Rebuffat S, Tieleman DP, Robinson CV, Beis Ket al., 2016, Structural and functional basis for lipid synergy on the activity of the antibacterial peptide ABC transporter McjD., J Biol Chem, ISSN: 0021-9258 Axford D, Foadi J, Hu N-J, Choudhury HG, Iwata S, Beis K, Evans G, Alguel Yet al., 2015, Structure determination of an integral membrane protein at room temperature from crystals in situ, ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, Vol: 71, Pages: 1228-1237, ISSN: 2059-7983 Beis K, 2015, Structural basis for the mechanism of ABC transporters, BIOCHEMICAL SOCIETY TRANSACTIONS, Vol: 43, Pages: 889-893, ISSN: 0300-5127 Gu R-X, Corradi V, Singh G, Beis K, Tieleman Pet al., 2015, Conformational Changes of the ABC Transporter McjD Revealed by Molecular Dynamics Simulations, BIOPHYSICAL JOURNAL, Vol: 108, Pages: 89A-89A, ISSN: 0006-3495 Gu R-X, Corradi V, Singh G, Choudhury HG, Beis K, Tieleman DPet al., 2015, Conformational Changes of the Antibacterial Peptide ATP Binding Cassette Transporter McjD Revealed by Molecular Dynamics Simulations, BIOCHEMISTRY, Vol: 54, Pages: 5989-5998, ISSN: 0006-2960 Choudhury HG, Tong Z, Mathavan I, Li Y, Iwata S, Zirah S, Rebuffat S, van Veen HW, Beis Ket al., 2014, Structure of an antibacterial peptide ATP-binding cassette transporter in a novel outward occluded state, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 111, Pages: 9145-9150, ISSN: 0027-8424 Lee C, Kang HJ, Hjelm A, Qureshi AA, Nji E, Choudhury H, Beis K, de Gier J-W, Drew Det al., 2014, MemStar: A one-shot Escherichia coli-based approach for high-level bacterial membrane protein production, FEBS LETTERS, Vol: 588, Pages: 3761-3769, ISSN: 0014-5793 Mathavan I, Zirah S, Mehmood S, Choudhury HG, Goulard C, Li Y, Robinson CV, Rebuffat S, Beis Ket al., 2014, Structural basis for hijacking siderophore receptors by antimicrobial lasso peptides, NATURE CHEMICAL BIOLOGY, Vol: 10, Pages: 340-U123, ISSN: 1552-4450 Choudhury HG, Beis K, 2013, The dimeric form of the unphosphorylated response regulator BaeR, PROTEIN SCIENCE, Vol: 22, Pages: 1287-1293, ISSN: 0961-8368 Choudhury HG, Beis K, 2013, Tellurite-Detoxifying Protein TehB from Escherichia coli, Encyclopedia of Metalloproteins, Editors: Kretsinger, Uversky, Permyakov, Publisher: Springer, ISBN: 978-1-4614-1532-9 Choudhury HG, Beis K, 2013, Tellurite-Resistance Protein TehA from Escherichia coli, Encyclopedia of Metalloproteins, Editors: Kretsinger, Uversky, Permyakov, Publisher: Springer, ISBN: 978-1-4614-1532-9 Corbalan N, Runti G, Adler C, Covaceuszach S, Ford RC, Lamba D, Beis K, Scocchi M, Vincent PAet al., 2013, Functional and Structural Study of the Dimeric Inner Membrane Protein SbmA, JOURNAL OF BACTERIOLOGY, Vol: 195, Pages: 5352-5361, ISSN: 0021-9193 Runti G, Ruiz MDCL, Stoilova T, Hussain R, Jennions M, Choudhury HG, Benincasa M, Gennaro R, Beis K, Scocchi Met al., 2013, Functional Characterization of SbmA, a Bacterial Inner Membrane Transporter Required for Importing the Antimicrobial Peptide Bac7(1-35), JOURNAL OF BACTERIOLOGY, Vol: 195, Pages: 5343-5351, ISSN: 0021-9193 Mathavan I, Beis K, 2012, The role of bacterial membrane proteins in the internalization of microcin MccJ25 and MccB17, BIOCHEMICAL SOCIETY TRANSACTIONS, Vol: 40, Pages: 1539-1543, ISSN: 0300-5127 Choudhury HG, Cameron AD, Iwata S, Beis Ket al., 2011, Structure and mechanism of the chalcogen-detoxifying protein TehB from Escherichia coli, BIOCHEMICAL JOURNAL, Vol: 435, Pages: 85-91, ISSN: 0264-6021 Choudhury HG, Cameron AD, Iwata S, Beis Ket al., 2011, Escherichia coli detoxification of chalcolgens by TehAB, 36th FEBS Congress of the Biochemistry for Tomorrows Medicine, Publisher: WILEY-BLACKWELL, Pages: 101-101, ISSN: 1742-464X Lou H, Chen M, Black SS, Bushell SR, Ceccarelli M, Mach T, Beis K, Low AS, Bamford VA, Booth IR, Bayley H, Naismith JHet al., 2011, Altered antibiotic transport in OmpC mutants isolated from a series of clinical strains of multi-drug resistant E. coli., PLoS One, Vol: 6 Sonoda Y, Newstead S, Hu N-J, Alguel Y, Nji E, Beis K, Yashiro S, Lee C, Leung J, Cameron AD, Byrne B, Iwata S, Drew Det al., 2011, Benchmarking Membrane Protein Detergent Stability for Improving Throughput of High-Resolution X-ray Structures, STRUCTURE, Vol: 19, Pages: 17-25, ISSN: 0969-2126 Beale J, Lee SY, Iwata S, Beis Ket al., 2010, Structure of the aliphatic sulfonate-binding protein SsuA from Escherichia coli, ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY AND CRYSTALLIZATION COMMUNICATIONS, Vol: 66, Pages: 391-396, ISSN: 1744-3091 Bushell SR, Lou H, Wallat GD, Beis K, Whitfield C, Naismith JHet al., 2010, Crystallization and preliminary diffraction analysis of Wzi, a member of the capsule export and assembly pathway in Escherichia coli, ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY AND CRYSTALLIZATION COMMUNICATIONS, Vol: 66, Pages: 1621-1625, ISSN: 1744-3091