Denise Wootten

Assoc Professor

Accepting PhD Students

20062023
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Research Output 2006 2018

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2018

Characterization of signalling and regulation of common calcitonin receptor splice variants and polymorphisms

Dal Maso, E., Just, R., Hick, C., Christopoulos, A., Sexton, P. M., Wootten, D. & Furness, S. G. B., 1 Feb 2018, In : Biochemical Pharmacology. 148, p. 111-129 19 p.

Research output: Contribution to journalArticleResearchpeer-review

Extracellular loops 2 and 3 of the calcitonin receptor selectively modify agonist binding and efficacy

Dal Maso, E., Zhu, Y., Pham, V., Reynolds, C. A., Deganutti, G., Hick, C. A., Yang, D., Christopoulos, A., Hay, D. L., Wang, M. W., Sexton, P. M., Furness, S. G. B. & Wootten, D., 1 Apr 2018, In : Biochemical Pharmacology. 150, p. 214-244 31 p.

Research output: Contribution to journalArticleResearchpeer-review

Open Access
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Glucagon-like peptide-1 receptor internalisation controls spatiotemporal signalling mediated by biased agonists

Fletcher, M. M., Halls, M. L., Zhao, P., Clydesdale, L., Christopoulos, A., Sexton, P. M. & Wootten, D., 1 Oct 2018, In : Biochemical Pharmacology. 156, p. 406-419 14 p.

Research output: Contribution to journalArticleResearchpeer-review

Phase-plate cryo-EM structure of a biased agonistbound human GLP-1 receptor-Gs complex

Liang, Y. L., Khoshouei, M., Glukhova, A., Furness, S. G. B., Zhao, P., Clydesdale, L., Koole, C., Truong, T. T., Thal, D. M., Lei, S., Radjainia, M., Danev, R., Baumeister, W., Wang, M. W., Miller, L. J., Christopoulos, A., Sexton, P. M. & Wootten, D., 1 Mar 2018, In : Nature. 555, 7694, p. 121-125 5 p.

Research output: Contribution to journalArticleResearchpeer-review

Open Access
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Structure of the adenosine-bound human adenosine A1 receptor-Gi complex

Draper-Joyce, C. J., Khoshouei, M., Thal, D. M., Liang, Y. L., Nguyen, A. T. N., Furness, S. G. B., Venugopal, H., Baltos, J. A., Plitzko, J. M., Danev, R., Baumeister, W., May, L. T., Wootten, D., Sexton, P. M., Glukhova, A. & Christopoulos, A., 20 Jun 2018, In : Nature. 558, 7711, p. 559-565 7 p.

Research output: Contribution to journalArticleResearchpeer-review

Two distinct domains of the glucagon-like peptide-1 receptor control peptide-mediated biased agonism

Lei, S., Clydesdale, L., Dai, A., Cai, X., Yang, F., Yang, D., Liang, Y-L., Koole, C., Zhao, P., Coudrat, T., Christopoulos, A., Wang, M-W., Wootten, D. & Sexton, P. M., 1 Jan 2018, In : Journal of Biological Chemistry. 293, 24, p. 9370-9387 18 p.

Research output: Contribution to journalArticleResearchpeer-review

Vascular and molecular pharmacology of the metabolically stable CGRP analogue, SAX

Sheykhzade, M., Abdolalizadeh, B., Koole, C., Pickering, D. S., Dreisig, K., Johansson, S. E., Abboud, B. K., Dreier, R., Berg, J. O., Jeppesen, J. L., Sexton, P. M., Edvinsson, L., Wootten, D. & Sams, A., 15 Jun 2018, In : European Journal of Pharmacology. 829, p. 85-92 8 p.

Research output: Contribution to journalArticleResearchpeer-review

2017

Characterization of signal bias at the GLP-1 receptor induced by backbone modification of GLP-1

Hager, M. V., Clydesdale, L., Gellman, S. H., Sexton, P. M. & Wootten, D., 15 Jul 2017, In : Biochemical Pharmacology. 136, p. 99-108 10 p.

Research output: Contribution to journalArticleResearchpeer-review

Co-expressed class B G protein-coupled secretin and GLP-1 receptors self- and cross-associate: impact on pancreatic islets

Harikumar, K. G., Lau, S., Sexton, P. M., Wootten, D. & Miller, L. J., 1 Jun 2017, In : Endocrinology. 158, 6, p. 1685-1700 16 p.

Research output: Contribution to journalArticleResearchpeer-review

Improving virtual screening of G protein-coupled receptors via ligand-directed modeling

Coudrat, T., Simms, J., Christopoulos, A., Wootten, D. & Sexton, P. M., 1 Nov 2017, In : PLoS Computational Biology. 13, 11, 40 p., e1005819.

Research output: Contribution to journalArticleResearchpeer-review

Open Access
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Phase-plate cryo-EM structure of a class B GPCR-G-protein complex

Liang, Y-L., Khoshouei, M., Radjainia, M., Zhang, Y., Glukhova, A., Tarrasch, J., Thal, D., Furness, S. G. B., Christopoulos, G., Coudrat, T., Danev, R., Baumeister, W., Miller, L. J., Christopoulos, A., Kobilka, B., Wootten, D., Skiniotis, G. & Sexton, P., 1 Jun 2017, In : Nature. 546, 7656, p. 118-123 6 p.

Research output: Contribution to journalArticleResearchpeer-review

Structural features embedded in G protein-coupled receptor co-crystal structures are key to their success in virtual screening

Coudrat, T., Christopoulos, A., Sexton, P. M. & Wootten, D., 1 Apr 2017, In : PLoS ONE. 12, 4, 29 p., e0174719.

Research output: Contribution to journalArticleResearchpeer-review

File
2016

A hydrogen-bonded polar network in the core of the glucagon-like peptide-1 receptor is a fulcrum for biased agonism: lessons from class B crystal structuress

Wootten, D., Reynolds, C. A., Koole, C., Smith, K. J., Mobarec, J. C., Simms, J., Quon, T., Coudrat, T., Furness, S. G. B., Miller, L. J., Christopoulos, A. & Sexton, P. M., 1 Mar 2016, In : Molecular Pharmacology. 89, 3, p. 335-347 13 p.

Research output: Contribution to journalArticleResearchpeer-review

Glucagon-like peptide-1 and its class B G protein-coupled receptors: a long march to therapeutic successes

de Graaf, C., Donnelly, D., Wootten, D., Lau, J., Sexton, P. M., Miller, L. J., Ahn, J-M., Liao, J., Fletcher, M. M., Yang, D., Brown, A. J. H., Zhou, C., Deng, J. & Wang, M-W., 1 Oct 2016, In : Pharmacological Reviews. 68, 4, p. 954-1013 60 p.

Research output: Contribution to journalArticleResearchpeer-review

Ligand-dependent modulation of G protein conformation alters drug efficacy

Furness, S. G. B., Liang, Y-L., Nowell, C. J., Halls, M. L., Wookey, P. J., Dal Maso, E., Inoue, A., Christopoulos, A., Wootten, D. & Sexton, P. M., 20 Oct 2016, In : Cell. 167, 3, p. 739-749 11 p.

Research output: Contribution to journalArticleResearchpeer-review

Monotreme glucagon-like peptide-1 in venom and gut: one gene - two very different functions

Tsend-Ayush, E., He, C., Myers, M. A., Andrikopoulos, S., Wong, N., Sexton, P. M., Wootten, D., Forbes, B. E. & Grutzner, F., 29 Nov 2016, In : Scientific Reports. 6, 12 p., 37744.

Research output: Contribution to journalArticleResearchpeer-review

Open Access
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Prediction of loops in G protein-coupled receptor homology models: effect of imprecise surroundings and constraints

Arora, B., Coudrat, T., Wootten, D., Christopoulos, A., Noronha, S. B. & Sexton, P. M., 25 Apr 2016, In : Journal of Chemical Information and Modeling. 56, 4, p. 671-686 16 p.

Research output: Contribution to journalArticleResearchpeer-review

The complexity of signalling mediated by the glucagon-like peptide-1 receptor

Fletcher, M. M., Halls, M. L., Christopoulos, A., Sexton, P. M. & Wootten, D., 15 Apr 2016, In : Biochemical Society Transactions. 44, 2, p. 582-588 7 p.

Research output: Contribution to journalArticleResearchpeer-review

The extracellular surface of the GLP-1 receptor is a molecular trigger for biased agonism

Wootten, D., Reynolds, C. A., Smith, K. J., Mobarec, J. C., Koole, C., Savage, E. E., Pabreja, K., Simms, J., Sridhar, R., Furness, S. G. B., Liu, M., Thompson, P. E., Miller, L. J., Christopoulos, A. & Sexton, P. M., 16 Jun 2016, In : Cell. 165, 7, p. 1632-1643 12 p.

Research output: Contribution to journalArticleResearchpeer-review

β-arrestin-biased agonists of the GLP-1 receptor from β-amino acid residue incorporation into GLP-1 analogues

Hager, M. V., Johnson, L. M., Wootten, D., Sexton, P. M. & Gellman, S. H., 16 Nov 2016, In : Journal of the American Chemical Society. 138, 45, p. 14970-14979 10 p.

Research output: Contribution to journalArticleResearchpeer-review

2014

Molecular mechanisms underlying physiological and receptor pleiotropic effects mediated by GLP-1R activation

Pabreja, K., Mohd, M., Koole, C. R., Wootten, D. L. & Furness, S. G. B., 2014, In : British Journal of Pharmacology. 171, 5, p. 1114 - 1128 15 p.

Research output: Contribution to journalArticleResearchpeer-review

Open Access
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Structural and functional insights into the juxtamembranous amino-terminal tail and extracellular loop regions of class B GPCRs

Dong, M., Koole, C. R., Wootten, D. L., Sexton, P. & Miller, L. J., 2014, In : British Journal of Pharmacology. 171, 5, p. 1085 - 1101 17 p.

Research output: Contribution to journalArticleResearchpeer-review

2013

A simple method to generate stable cell lines for the analysis of transient protein-protein interactions

Savage, E. E., Wootten, D. L., Christopoulos, A., Sexton, P. & Furness, S. G. B., 2013, In : BioTechniques. 54, 4, p. 217 - 221 5 p.

Research output: Contribution to journalArticleResearchpeer-review

Open Access
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Differential activation and modulation of the glucagon-like peptide-1 receptor by small molecule ligands

Wootten, D. L., Savage, E. E., Willard, F. S., Bueno, A. B., Sloop, K. W., Christopoulos, A. & Sexton, P., 2013, In : Molecular Pharmacology. 83, 4, p. 822 - 834 13 p.

Research output: Contribution to journalArticleResearchpeer-review

Emerging paradigms in GPCR allostery: implications for drug discovery

Wootten, D. L., Christopoulos, A. & Sexton, P., 2013, In : Nature Reviews Drug Discovery. 12, 8, p. 630 - 644 15 p.

Research output: Contribution to journalArticleResearchpeer-review

Minireview: Signal bias, allosterism, and polymorphic variation at the GLP-1R: implications for drug discovery

Koole, C. R., Savage, E. E., Christopoulos, A., Miller, L. J., Sexton, P. & Wootten, D. L., 2013, In : Molecular Endocrinology. 27, 8, p. 1234 - 1244 11 p.

Research output: Contribution to journalArticleResearchpeer-review

Polar transmembrane interactions drive formation of ligand-specific and signal pathway-biased family B G protein-coupled receptor conformations

Wootten, D. L., Simms, J. W., Miller, L. J., Christopoulos, A. & Sexton, P., 2013, In : Proceedings of the National Academy of Sciences. 110, 13, p. 5211 - 5216 6 p.

Research output: Contribution to journalArticleResearchpeer-review

Open Access

Recent advances in understanding GLP-1R (glucagon-like peptide-1 receptor) function

Koole, C. R., Pabreja, K., Savage, E. E., Wootten, D. L., Furness, S. G. B., Miller, L. J., Christopoulos, A. & Sexton, P., 2013, In : Biochemical Society Transactions. 41, 1, p. 172 - 179 8 p.

Research output: Contribution to journalArticleResearchpeer-review

Receptor activity-modifying protein-dependent impairment of calcitonin receptor splice variant Delta(1-47)hCT((a)) function

Qi, T., Dong, M. DONG., Watkins, H. A., Wootten, D. L., Miller, L. J. & Hay, D. L., 2013, In : British Journal of Pharmacology. 168, 3, p. 644 - 657 14 p.

Research output: Contribution to journalArticleResearchpeer-review

Receptor activity modifying proteins (RAMPs) interact with the VPAC 2 receptor and CRF1 receptors and modulate their function

Wootten, D. L., Lindmark, H., Kadmiel, M., Willcockson, H. H., Caron, K. M., Barwell, J., Drmota, T. & Poyner, D. R., 2013, In : British Journal of Pharmacology. 168, 4, p. 822 - 834 13 p.

Research output: Contribution to journalArticleResearchpeer-review

2012

Allosteric modulation of endogenous metabolites as an avenue for drug discovery

Wootten, D. L., Savage, E. E., Valant, C., May, L. T., Sloop, K. W., Ficorilli, J., Showalter, A. D., Willard, F. S., Christopoulos, A. & Sexton, P. M., 2012, In : Molecular Pharmacology. 82, 2, p. 281 - 290 10 p.

Research output: Contribution to journalArticleResearchpeer-review

Consequences of splice variation on secretin family G protein-coupled receptor function

Furness, S. G. B., Wootten, D. L., Christopoulos, A. & Sexton, P. M., 2012, In : British Journal of Pharmacology. 166, 1, p. 98 - 109 12 p.

Research output: Contribution to journalArticleResearchpeer-review

Open Access
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Glucagon-like peptide-1 receptor dimerization differentially regulates agonist signaling but does not affect small molecule allostery

Harikumar, K. G., Wootten, D. L., Pinon, D. I., Koole, C. R., Ball, A. M., Furness, S. GB., Graham, B., Dong, M., Christopoulos, A., Miller, L. J. & Sexton, P. M., 2012, In : Proceedings of the National Academy of Sciences. 109, 45, p. 18607 - 18612 6 p.

Research output: Contribution to journalArticleResearchpeer-review

Open Access
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Lifting the lid on GPCRs: the role of extracellular loops

Wheatley, M., Wootten, D. L., Conner, M., Simms, J. W., Kendrick, R., Logan, R. T., Poyner, D. R. & Barwell, J., 2012, In : British Journal of Pharmacology. 165, 6, p. 1688 - 1703 16 p.

Research output: Contribution to journalArticleResearchpeer-review

Second extracellular loop of human glucagon-like peptide-1 receptor (GLP-1R) differentially regulates orthosteric but not allosteric agonist binding and function

Koole, C. R., Wootten, D. L., Simms, J., Savage, E. E., Miller, L. J., Christopoulos, A. & Sexton, P. M., 2012, In : Journal of Biological Chemistry. 287, 6, p. 3659 - 3673 15 p.

Research output: Contribution to journalArticleResearchpeer-review

Second extracellular loop of human glucagon-like peptide-1 receptor (GLP-1R) has a critical role in GLP-1 peptide binding and receptor activation

Koole, C. R., Wootten, D. L., Simms, J. W., Miller, L. J., Christopoulos, A. & Sexton, P., 2012, In : Journal of Biological Chemistry. 287, 6, p. 3642 - 3658 17 p.

Research output: Contribution to journalArticleResearchpeer-review

Small molecule allosteric modulation of the glucagon-like Peptide-1 receptor enhances the insulinotropic effect of oxyntomodulin

Willard, F. S., Wootten, D. L., Showalter, A. D., Savage, E. E., Ficorilli, J., Farb, T. B., Bokvist, K., Alsina-Fernandez, J., Furness, S. GB., Christopoulos, A., Sexton, P. M. & Sloop, K. W., 2012, In : Molecular Pharmacology. 82, 6, p. 1066 - 1073 8 p.

Research output: Contribution to journalArticleResearchpeer-review

2011

Agonist-specific requirement for a glutamate in transmembrane helix 1 of the oxytocin receptor

Wootten, D. L., Simms, J., Massoura, A. J., Trim, J. E. & Wheatley, M., 10 Feb 2011, In : Molecular and Cellular Endocrinology. 333, 1, p. 20-27 8 p.

Research output: Contribution to journalArticleResearchpeer-review

Modulation of the glucagon-like peptide-1 receptor signaling by naturally occurring and synthetic flavonoids

Wootten, D., Simms, J., Koole, C., Woodman, O., Summers, R., Christopoulos, A. & Sexton, P., 2011, In : Journal of Pharmacology and Experimental Therapeutics. 336, 2, p. 540 - 550 11 p.

Research output: Contribution to journalArticleResearchpeer-review

Polymorphism and ligand dependent changes in human glucagon-like peptide-1 receptor (GLP-1R) function: allosteric rescue of loss of function mutation

Koole, C., Wootten, D., Simms, J., Valant, C., Miller, L. J., Christopoulos, A. & Sexton, P., 2011, In : Molecular Pharmacology. 80, 3, p. 486 - 497 12 p.

Research output: Contribution to journalArticleResearchpeer-review

Status of GPCR modeling and docking as reflected by community-wide GPCR Dock 2010 assessment

Kufareva, I., Rueda, M., Katritch, V., Stevens, R. C., Abagyan, R., McRobb, F. M., Capuano, B., Crosby, I. T., Chalmers, D. K., Yuriev, E., Simms, J. W., Sexton, P., Wootten, D. L. & Hall, N. E., 2011, In : Structure. 19, 8, p. 1108 - 1126 19 p.

Research output: Contribution to journalArticleResearchpeer-review

2007

Extracellular loops and ligand binding to a subfamily of Family A G-protein-coupled receptors

Wheatley, M., Simms, J. W., Hawtin, S. R., Wesley, V. J., Wootten, D. L., Conner, M., Lawson, Z., Conner, A. C., Baker, A., Cashmore, Y., Kendrick, R. & Parslow, R. A., 2007, In : Biochemical Society Transactions. 35, Pt 4, p. 717 - 720 4 p.

Research output: Contribution to journalArticleResearchpeer-review

Systematic analysis of the entire second extracellular loop of the V 1a vasopressin receptor: Key residues, conserved throughout a G-protein-coupled receptor family, identified

Conner, M., Hawtin, S. R., Simms, J. W., Wootten, D. L., Lawson, Z., Conner, A. C., Parslow, R. A. & Wheatley, M., 2007, In : Journal of Biological Chemistry. 282, 24, p. 17405 - 17412 8 p.

Research output: Contribution to journalArticleResearchpeer-review

2006

Diverse functional motifs within the three intracellular loops of the CGRP1 receptor

Conner, A. C., Simms, J. W., Conner, M. T., Wootten, D. L., Wheatley, M. & Poyner, D. R., 2006, In : Biochemistry. 45, 43, p. 12976 - 12985 10 p.

Research output: Contribution to journalArticleResearchpeer-review