Amir Khan
Associate Professor, Biochemistry

Biography

Publications and Further Research Outputs

Peer-Reviewed Publications

Nounamo B, Li Y, O'Byrne P, Kearney A.M, Khan A, Liu J, An interaction domain in human SAMD9 is essential for myxoma virus host-range determinant M062 antagonism of host anti-viral function, Virology, 503, 2017, p94 - 102 Journal Article, 2017 DOI URL

Mulvaney E.P, O'Meara F, Khan A.R, O'Connell D.J, Kinsella B.T, Identification of α-helix 4 (α4) of Rab11a as a novel Rab11-binding domain (RBD): Interaction of Rab11a with the Prostacyclin Receptor, Biochimica et Biophysica Acta - Molecular Cell Research, 1864, (10), 2017, p1819 - 1832 Journal Article, 2017 URL DOI

Oliveira T, Sharkey M.A, Engel P.C, Khan A.R, Crystal structure of a chimaeric bacterial glutamate dehydrogenase, Acta Crystallographica Section:F Structural Biology Communications, 72, 2016, p462 - 466 Journal Article, 2016 URL DOI

Lall, P., Lindsay, A.J., Hanscom, S., (...), McCaffrey, M.W., Khan, A.R., Structure-function analyses of the interactions between Rab11 and Rab14 small GTPases with their shared effector Rab coupling protein (RCP), Journal of Biological Chemistry, 290, (30), 2015, 18817-18832 Journal Article, 2015 TARA - Full Text DOI

Lall, P., Horgan, C.P., Oda, S., (...), McCaffrey, M.W., Khan, A.R., Structural and functional analysis of FIP2 binding to the endosome-localised Rab25 GTPase, Biochimica et Biophysica Acta - Proteins and Proteomics , 1834, (12), 2013, p2679-2690 Journal Article, 2013 DOI

Khan AR, Oligomerization of rab/effector complexes in the regulation of vesicle trafficking., Progress in molecular biology and translational science, 117, 2013, p579-614 Journal Article, 2013 DOI

Khan, A.R., Ménétrey, J., Structural biology of arf and rab GTPases' effector recruitment and specificity, Structure , 21, (8), 2013, p1284-1297 Journal Article, 2013 TARA - Full Text DOI

Franklin, E., Khan, A.R., Poxvirus antagonism of innate immunity by Bcl-2 fold proteins, Journal of Structural Biology, 181, (1), 2013, p1-10 Journal Article, 2013 DOI

Sharkey MA, Oliveira TF, Engel PC, Khan AR, Structure of NADP(+)-dependent glutamate dehydrogenase from Escherichia coli--reflections on the basis of coenzyme specificity in the family of glutamate dehydrogenases., The FEBS journal, 280, (18), 2013, p4681-92 Journal Article, 2013 DOI

Stack, J., Hurst, T.P., Flannery, S.M., (...), Khan, A.R., Bowie, A.G. , Poxviral protein A52 stimulates p38 mitogen-activated protein kinase (MAPK) activation by causing tumor necrosis factor receptor-associated factor 6 (TRAF6) self-association leading to transforming growth factor β-activated kinase 1 (TAK1) recruitment, Journal of Biological Chemistry, 288, (47), 2013, p33642-33653 Journal Article, 2013 DOI

Fernandes, H., Franklin, E., Jollivet, F., Bliedtner, K., Khan, A.R., Mapping the interactions between a RUN domain from DENND5/Rab6IP1 and sorting nexin 1., PloS one, 7, (4), 2012, pe35637 Journal Article, 2012 DOI TARA - Full Text

Tânia Oliveira, Santosh Panjikar, John B. Carrigan, Muaawia Hamza, Paul C. Engel, Amir R. Khan, Crystal Structure of NAD-dependent Peptoniphilus Asaccharolyticus Glutamate Dehydrogenase Reveals Determinants of Cofactor Specificity, Journal of Structural Biology, 177, (2), 2012, p543-552 Journal Article, 2012 TARA - Full Text

McGovern, R.E., Fernandes, H., Khan, A.R., Power, N.P., Crowley, P.B., Protein camouflage in cytochrome c-calixarene complexes, Nature Chemistry, 4, (7), 2012, p527-533 Journal Article, 2012 DOI

Fernandes H, Franklin E, Khan AR, Crystallization of an engineered RUN domain of Rab6-interacting protein 1/DENND5., Acta Crystallographica. Section F, Structural Biology and Crystallization Communications, 67, (Pt 5), 2011, p556-60 Journal Article, 2011 TARA - Full Text DOI

Shun-ichiro Oda, Edward Franklin, Amir R. Khan, Poxvirus A46 protein binds to TIR domain-containing Mal/TIRAP via an a-helical sub-domain, Molecular Immunology, 48, 2011, p2144 - 2150 Journal Article, 2011 DOI

Tânia F. Oliveira, Edward Franklin, José P. Afonso, Amir R. Khan, Neil J. Oldham, Inês A. C. Pereira and Margarida Archer, Structural insights into dissimilatory sulfite reductases: structure of desulforubidin from Desulfomicrobium norvegicum, Frontiers in Microbial Physiology and Metabolism, 2, (71), 2011 Journal Article, 2011 TARA - Full Text

Jin, Y., Sultana, A., Gandhi, P., Franklin, E., Hamamoto, S., Khan, A.R., Munson, M., (...), Weisman, L.S., Myosin V transports secretory vesicles via a Rab GTPase cascade and interaction with the exocyst complex, Developmental Cell, 21, (6), 2011, p1156-1170 Journal Article, 2011 DOI

Sultana, A., Jin, Y., Dregger, C., Franklin, E., Weisman, L.S., Khan, A.R., The activation cycle of Rab GTPase Ypt32 reveals structural determinants of effector recruitment and GDI binding, FEBS Letters, 585, (22), 2011, 3520-3527 Journal Article, 2011 DOI

Oliveira, T.F., Carrigan, J.B., Hamza, M.A., Sharkey, M.A., Engel, P.C., Khan, A.R., Crystallization and preliminary structural analyses of glutamate dehydrogenase from Peptoniphilus asaccharolyticus, Acta Crystallographica Section F: Structural Biology and Crystallization Communications, 66, (5), 2010, p523-526 Journal Article, 2010 DOI

Nagle PS, Quinn SJ, Kelly JM, O'Donovan DH, Khan AR, Rodriguez F, Nguyen B, Wilson WD, Rozas I, Understanding the DNA binding of novel non-symmetrical guanidinium/2-aminoimidazolinium derivatives., Organic & Biomolecular chemistry, 8, (24), 2010, p5558-67 Journal Article, 2010 TARA - Full Text DOI

Recacha R, Boulet A, Jollivet F, Monier S, Houdusse A, Goud B & Khan AR , Structural basis for recruitment of Rab6-Interacting Protein 1 to Golgi via a RUN domain., Structure, 17, (1), 2009, p21-30 Journal Article, 2009 URL DOI

Kalverda AP, Thompson GS, Vogel A, Schröder M, Bowie AG, Khan AR & Homans SW, Poxvirus K7 protein adopts a Bcl-2 fold: Biochemical mapping of its interactions with human DEAD box RNA helicase DDX3., Journal of Molecular Biology, 385, (3), 2009, p843-853 Journal Article, 2009 URL DOI

Fernandes, H., Franklin, E., Recacha, R., Houdusse, A., Goud, B., Khan, A.R., Structural aspects of Rab6-effector complexes, Biochemical Society Transactions, 37, (5), 2009, p1037-1041 Journal Article, 2009 DOI

Crowley, P.B., Matias, P.M., Khan, A.R., Roessle, M., Svergun, D.I., Metal-mediated self-assembly of a β-sandwich protein, Chemistry - A European Journal , 15, (46), 2009, p12672-12680 Journal Article, 2009 DOI

Shun-ichiro Oda, Martina Schroder, Amir R. Khan, Structural Basis for Targeting of Human RNA Helicase DDX3 by Poxvirus Protein K7, Structure (Cell Press), 17, 2009, p1528 - 1537 Journal Article, 2009

Horgan CP, Oleksy1 A, Alexander V. Zhdanov AV, Lall PY, Ian J. White, Khan AR, Futter CE, McCaffrey JG & McCaffrey MW, Rab11-FIP3 is critical for the structural integrity of the endosomal-recycling compartment., Traffic, 8, (1), 2007, p414-430 Journal Article, 2007 DOI URL

Khor CC, Chapman SJ, Vannberg FO, Dunne A, Murphy C, Ling EY, Frodsham AJ, Walley AJ, Kyrieleis O, Khan A, Aucan C, Segal S, Moore CE, Knox K, Campbell SJ, Lienhardt C, Scott A, Aaby P, Sow OY, Grignani RT, Sillah J, Sirugo G, Peshu N, Williams TN, Maitland K, Davies RJ, Kwiatkowski DP, Day NP, Yala D, Crook DW, Marsh K, Berkley JA, O'Neill LA, Hill AV., A Mal functional variant is associated with protection against invasive pneumococcal disease, bacteremia, malaria and tuberculosis., Nature Genetics, 39, (4), 2007, p523-8 Journal Article, 2007 DOI URL

Jagoe WN, Jackson SR, Lindsay AJ, McCaffrey MW & Khan AR, Purification, crystallization, and preliminary X-ray diffraction studies of Rab11 in complex with Rab11-FIP2, Acta Crystallogr Sect F Struct Biol Cryst Commun. , 62, (7), 2006, p692 - 694 Journal Article, 2006 URL DOI

Jagoe WN, Lindsay AJ, Read RJ, McCoy AJ, McCaffrey MW & Khan AR, Crystal structure of Rab11 in complex with Rab11 Family Interacting Protein 2, Structure (Cell Press), 14, (8), 2006, p1273 - 1283 Journal Article, 2006 DOI URL URL

Chen M, Stafford W, Diedrich G, Khan AR and Bouvier M, A characterization of the lumenal region of human tapasin reveals the presence of two structural domains., Biochemistry, 41, (49), 2002, p14539 - 14545 Journal Article, 2002 DOI URL

Khan AR, Khazanovich-Bernstein N, Bergmann EM & James MNG , Structural aspects of the activation pathways of aspartic protease zymogens and viral 3C protease zymogens. , Proc Natl Acad Sci USA , 96, (20), 1999, p10968 - 10975 Journal Article, 1999 URL

Mark BL, Wasney GA, Salo T, Khan AR, Cao Z, Robbins PW, James MNG & Triggs-Laine BL , Structural and functional characterization of Streptomyces plicatus Beta-N-acetylhexosaminidase by comparative molecular modelling and site-directed mutagenesis, Journal of Biological Chemistry , 273, (31), 1998, p19618 - 19624 Journal Article, 1998 URL

Crystallographic studies of an activation intermediate of human gastricsin. in, editor(s)MNG James , The Aspartic Proteinases: Retroviral and Cellular Enzymes , New York, Plenum Press, 1998, pp265 - 270., [Amir Khan] Book Chapter, 1998

Khan AR & James MNG , Molecular mechanisms for the conversion of zymogens to active proteolytic enzymes, Protein Science, 7, (4), 1998, p815 - 836 Journal Article, 1998 URL

Khan AR, Parrish JC, Fraser ME, Smith WW, Bartlett PA & James MNG, Lowering the entropic barrier for binding conformationally flexible inhibitors to enzymes. , Biochemistry, 37, (48), 1998, p16839 - 16845 Journal Article, 1998 DOI URL

Khan AR, Cherney MM, Tarasova NI & James MNG , Structural characterization of activation 'intermediate 2' on the pathway to human gastricsin, Nature Structural Biology , 4, (12), 1997, p1010 - 1015 Journal Article, 1997 URL DOI

Khan AR, Johnson KA, Braam J & James MNG, Comparative molecular modelling of the three-dimensional structure of calmodulin-related TCH2 protein from Arabidopsis, Proteins: Structure, Function and Genetics , 27, (1), 1997, p144 - 153 Journal Article, 1997 DOI URL

Khan, A.R., Chernaia, M.M., Tarasova, N.I. , Structure of folding intermediate during activation of an aspartic proteinase zymogen, FASEB Journal, 11, (9), 1997, pA1396 Journal Article, 1997

Williams KA, Glibowicka M, Li Z, Li H, Khan AR, Chen YM, Wang J, Marvin DA & Deber CM, Role of small residues in filamentous phage packing. , Journal of Molecular Biology , 252, (1), 1995, p6 - 14 Journal Article, 1995 URL DOI

Khan AR & Deber CM, An engineered disulfide bridge in the transmembrane region of phage M13 coat protein stabilizes the omega-helical dimer., Biochemical and Biophysical Research Communications , 206, (1), 1995, p230 - 237 Journal Article, 1995 DOI URL

Khan AR, Williams KA, Boggs JM & Deber CM , Accessibility and dynamics of viable Cys mutants of phage IKe and M13 major coat proteins, Biochemistry, 34, (38), 1995, p12388 - 12397 Journal Article, 1995 DOI URL

Deber CM, Khan AR, Li Z, Joensson C, Glibowicka M & Wang J, Val to Ala mutations selectively alter helix-helix packing in the transmembrane segment of phage M13 coat protein, Proc Natl Acad Sci USA, 90, (20), 1993, p11648 - 11652 Journal Article, 1993 URL

Research Expertise

Description

The experimental goal is determination of structures of Rabs with their effector proteins by X-ray crystallography. The first project will involve Rab6, which regulates the forward and retrograde transport pathways at the level of Golgi membranes. The downstream effects of Rab6 are mediated by Rab6IP1, a 1263-residue Rab6IP1 that contains several novel domains for which there is no structural information in the Protein Data Bank. The second project involves Rab11, which is involved in endocytic recycling processes, as well as endosome-to-Golgi trafficking. One of its effectors is FIP2, which belongs to a family of proteins that contain a conserved C-terminal Rab-binding domain. The structures of these effectors may have novel folds, and the complexes with their respective Rabs are likely to demonstrate novel modes of interaction. In addition, the structure of the complex will enable a generalization of the mechanism of Rab family-mediated signaling, since the domains observed in Rab6IP1 are also found in a variety of other mammalian proteins.

Projects

  • Title
    • X-ray Crystallographic Studies of Poxvirus-Mediated Antagonism of TLR signaling
  • Summary
    • Toll-like receptors (TLRs) are essential components of innate immunity against bacterial and viral pathogens. The ten TLRs in humans recognize broad types of pathogen associated molecular patterns (PAMPs) including nucleic acids and lipopolysaccharides. The signaling cascade is initiated by their intracellular Toll-like/interleukin-1 receptor (TIR) domains which oligomerize and recruit TIR-containing adaptor proteins such as MyD88 to mediate downstream events. Viruses often attenuate immune responses, and recently, vaccinia virus proteins A46R, A52R and K7R have been shown to antagonize TLR signaling pathways. Interestingly, A46R contains a putative TIR domain that binds to MyD88 and blocks TLR activation, in contrast to the TIR domains of TLRs which promote the signaling cascade. The project described here will involve X-ray crystallographic studies of poxvirus proteins A46R, A52R and K7R alone and in complex with their cellular targets in order to understand the molecular basis for antagonism of TLR signaling.
  • Funding Agency
    • Science Foundation Ireland
  • Date From
    • 1/10/2005
  • Date To
    • 31/9/2008

Keywords

CONGENITAL HEMANGIOPERICYTOMA; EXTERNAL CAROTID ARTERY LIGATION; LIFE-THREATENING HEMORRHAGE

Recognition

Awards and Honours

Research Grant - SFI Frontiers Programme 2005

Cyril M. Kay Book Prize in Biochemistry University of Alberta 1995

Studentship, Medical Research Council of Canada 1996

Student Travel Award, American Crystallographic Association St. Louis, MI 1997

Finn Wold Travel Award, Eleventh Symposium of the Protein Society, Boston, MA 1997

Dissertation Fellowship, University of Alberta 1998

Graduate Student Poster Prize, CFBS Annual Meeting Edmonton, Alberta 1998

Fellowship, Human Frontiers Science Program 1999

Fellowship, Centre National de la Recherche Scientifique (CNRS), France 2001

Fellowship, Canadian Institutes of Health Research (CIHR) 2002

Research Grant, Scientific Investigator Programme, Science Foundation Ireland 2004