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Title: Orthosteric and allosteric action of the C5a receptor antagonists

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Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
OSTI Identifier:
Resource Type:
Journal Article
Journal Name:
Nature Structural & Molecular Biology
Additional Journal Information:
Journal Volume: 25; Journal Issue: 6; Journal ID: ISSN 1545-9993
Nature Publishing Group
Country of Publication:
United States

Citation Formats

Liu, Heng, Kim, Hee Ryung, Deepak, R. N. V. Krishna, Wang, Lei, Chung, Ka Young, Fan, Hao, Wei, Zhiyi, and Zhang, Cheng. Orthosteric and allosteric action of the C5a receptor antagonists. United States: N. p., 2018. Web. doi:10.1038/s41594-018-0067-z.
Liu, Heng, Kim, Hee Ryung, Deepak, R. N. V. Krishna, Wang, Lei, Chung, Ka Young, Fan, Hao, Wei, Zhiyi, & Zhang, Cheng. Orthosteric and allosteric action of the C5a receptor antagonists. United States. doi:10.1038/s41594-018-0067-z.
Liu, Heng, Kim, Hee Ryung, Deepak, R. N. V. Krishna, Wang, Lei, Chung, Ka Young, Fan, Hao, Wei, Zhiyi, and Zhang, Cheng. Fri . "Orthosteric and allosteric action of the C5a receptor antagonists". United States. doi:10.1038/s41594-018-0067-z.
title = {Orthosteric and allosteric action of the C5a receptor antagonists},
author = {Liu, Heng and Kim, Hee Ryung and Deepak, R. N. V. Krishna and Wang, Lei and Chung, Ka Young and Fan, Hao and Wei, Zhiyi and Zhang, Cheng},
abstractNote = {},
doi = {10.1038/s41594-018-0067-z},
journal = {Nature Structural & Molecular Biology},
issn = {1545-9993},
number = 6,
volume = 25,
place = {United States},
year = {2018},
month = {6}

Works referenced in this record:

International Union of Basic and Clinical Pharmacology. LXXXVII. Complement Peptide C5a, C4a, and C3a Receptors
journal, January 2013

  • Klos, Andreas; Wende, Elisabeth; Wareham, Kathryn J.
  • Pharmacological Reviews, Vol. 65, Issue 1
  • DOI: 10.1124/pr.111.005223

Protein structure and dynamics studied by mass spectrometry: H/D exchange, hydroxyl radical labeling, and related approaches
journal, August 2008

  • Konermann, Lars; Tong, Xin; Pan, Yan
  • Journal of Mass Spectrometry, Vol. 43, Issue 8
  • DOI: 10.1002/jms.1435

Role of the carboxyl terminal di-leucine in phosphorylation and internalization of C5a receptor
journal, June 2008

  • Suvorova, Elena S.; Gripentrog, Jeannie M.; Oppermann, Martin
  • Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Vol. 1783, Issue 6
  • DOI: 10.1016/j.bbamcr.2008.02.004

Crystallizing Membrane Proteins for Structure Determination: Use of Lipidic Mesophases
journal, June 2009

Crystal structure of the chemokine receptor CXCR4 in complex with a viral chemokine
journal, January 2015

High-resolution crystal structure of human protease-activated receptor 1
journal, December 2012

  • Zhang, Cheng; Srinivasan, Yoga; Arlow, Daniel H.
  • Nature, Vol. 492, Issue 7429
  • DOI: 10.1038/nature11701

Comparative Agonist/Antagonist Responses in Mutant Human C5a Receptors Define the Ligand Binding Site
journal, January 2005

  • Higginbottom, Adrian; Cain, Stuart A.; Woodruff, Trent M.
  • Journal of Biological Chemistry, Vol. 280, Issue 18
  • DOI: 10.1074/jbc.M410797200

Two-site binding of C5a by its receptor: an alternative binding paradigm for G protein-coupled receptors.
journal, February 1994

  • Siciliano, S. J.; Rollins, T. E.; DeMartino, J.
  • Proceedings of the National Academy of Sciences, Vol. 91, Issue 4
  • DOI: 10.1073/pnas.91.4.1214

Potent Cyclic Antagonists of the Complement C5a Receptor on Human Polymorphonuclear Leukocytes. Relationships between Structures and Activity
journal, March 2004

  • March, Darren R.; Proctor, Lavinia M.; Stoermer, Martin J.
  • Molecular Pharmacology, Vol. 65, Issue 4
  • DOI: 10.1124/mol.65.4.868

Structural basis for the cooperative allosteric activation of the free fatty acid receptor GPR40
journal, June 2017

  • Lu, Jun; Byrne, Noel; Wang, John
  • Nature Structural & Molecular Biology, Vol. 24, Issue 7
  • DOI: 10.1038/nsmb.3417

Targeting the minor pocket of C5aR for the rational design of an oral allosteric inhibitor for inflammatory and neuropathic pain relief
journal, November 2014

  • Moriconi, Alessio; Cunha, Thiago M.; Souza, Guilherme R.
  • Proceedings of the National Academy of Sciences, Vol. 111, Issue 47
  • DOI: 10.1073/pnas.1417365111

MolProbity: More and better reference data for improved all-atom structure validation: PROTEIN SCIENCE.ORG
journal, November 2017

  • Williams, Christopher J.; Headd, Jeffrey J.; Moriarty, Nigel W.
  • Protein Science, Vol. 27, Issue 1
  • DOI: 10.1002/pro.3330

Inhibiting the C5–C5a receptor axis
journal, August 2011

Structure of the complement C5a receptor bound to the extra-helical antagonist NDT9513727
journal, January 2018

  • Robertson, Nathan; Rappas, Mathieu; Doré, Andrew S.
  • Nature, Vol. 553, Issue 7686
  • DOI: 10.1038/nature25025

C5a-Stimulated Recruitment of  -Arrestin2 to the Nonsignaling 7-Transmembrane Decoy Receptor C5L2
journal, July 2009

  • Van Lith, L. H. C.; Oosterom, J.; Van Elsas, A.
  • Journal of Biomolecular Screening, Vol. 14, Issue 9
  • DOI: 10.1177/1087057109341407

Structural basis for selectivity and diversity in angiotensin II receptors
journal, April 2017

  • Zhang, Haitao; Han, Gye Won; Batyuk, Alexander
  • Nature, Vol. 544, Issue 7650
  • DOI: 10.1038/nature22035

Fusion Partner Toolchest for the Stabilization and Crystallization of G Protein-Coupled Receptors
journal, June 2012

Complement C5a Receptor Facilitates Cancer Metastasis by Altering T-Cell Responses in the Metastatic Niche
journal, May 2014

Structure of the agonist-bound neurotensin receptor
journal, October 2012

  • White, Jim F.; Noinaj, Nicholas; Shibata, Yoko
  • Nature, Vol. 490, Issue 7421
  • DOI: 10.1038/nature11558

Structural Basis for Allosteric Regulation of GPCRs by Sodium Ions
journal, July 2012

Formyl peptide receptor-mediated ERK1/2 activation occurs through Gi and is not dependent on β-arrestin1/2
journal, February 2008

Contribution of complement activation pathways to neuropathology differs among mouse models of Alzheimer's disease
journal, January 2011

  • Fonseca, Maria I.; Chu, Shu-Hui; Berci, Alisia M.
  • Journal of Neuroinflammation, Vol. 8, Issue 1
  • DOI: 10.1186/1742-2094-8-4

Molecular Characterization of the Gerbil C5a Receptor and Identification of a Transmembrane Domain V Amino Acid That Is Crucial for Small Molecule Antagonist Interaction
journal, October 2005

  • Waters, Stephen M.; Brodbeck, Robbin M.; Steflik, Jeremy
  • Journal of Biological Chemistry, Vol. 280, Issue 49
  • DOI: 10.1074/jbc.M509245200

Function, structure and therapeutic potential of complement C5a receptors
journal, October 2007

  • Monk, P. N.; Scola, A-M; Madala, P.
  • British Journal of Pharmacology, Vol. 152, Issue 4
  • DOI: 10.1038/sj.bjp.0707332

Discovery of an irreversible HCV NS5B polymerase inhibitor
journal, December 2013

  • Zeng, Qingbei; Nair, Anilkumar G.; Rosenblum, Stuart B.
  • Bioorganic & Medicinal Chemistry Letters, Vol. 23, Issue 24
  • DOI: 10.1016/j.bmcl.2013.10.060

Activation mechanism of endothelin ETB receptor by endothelin-1
journal, September 2016

  • Shihoya, Wataru; Nishizawa, Tomohiro; Okuta, Akiko
  • Nature, Vol. 537, Issue 7620
  • DOI: 10.1038/nature19319

The role of the anaphylatoxins in health and disease
journal, September 2009

An Activation Switch in the Ligand Binding Pocket of the C5a Receptor
journal, November 2000

  • Gerber, Basil O.; Meng, Elaine C.; Dötsch, Volker
  • Journal of Biological Chemistry, Vol. 276, Issue 5
  • DOI: 10.1074/jbc.M007748200

Active immunization against complement factor C5a: a new therapeutic approach for Alzheimer’s disease
journal, August 2015

  • Landlinger, Christine; Oberleitner, Lisa; Gruber, Petra
  • Journal of Neuroinflammation, Vol. 12, Issue 1
  • DOI: 10.1186/s12974-015-0369-6

Identification of a Potent and Orally Active Non-peptide C5a Receptor Antagonist
journal, October 2002

  • Sumichika, Hiroshi; Sakata, Kei; Sato, Noriko
  • Journal of Biological Chemistry, Vol. 277, Issue 51
  • DOI: 10.1074/jbc.M209672200

Structural Basis for Apelin Control of the Human Apelin Receptor
journal, June 2017

Comprehensive repertoire and phylogenetic analysis of the G protein-coupled receptors in human and mouse
journal, September 2006

Structure of a nanobody-stabilized active state of the β2 adrenoceptor
journal, January 2011

  • Rasmussen, Søren G. F.; Choi, Hee-Jung; Fung, Juan Jose
  • Nature, Vol. 469, Issue 7329
  • DOI: 10.1038/nature09648

Modulation of the antitumor immune response by complement
journal, September 2008

  • Markiewski, Maciej M.; DeAngelis, Robert A.; Benencia, Fabian
  • Nature Immunology, Vol. 9, Issue 11
  • DOI: 10.1038/ni.1655

Structures of the CXCR4 Chemokine GPCR with Small-Molecule and Cyclic Peptide Antagonists
journal, October 2010

MolProbity : all-atom structure validation for macromolecular crystallography
journal, December 2009

  • Chen, Vincent B.; Arendall, W. Bryan; Headd, Jeffrey J.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 1
  • DOI: 10.1107/S0907444909042073

Two disparate ligand-binding sites in the human P2Y1 receptor
journal, March 2015

  • Zhang, Dandan; Gao, Zhan-Guo; Zhang, Kaihua
  • Nature, Vol. 520, Issue 7547
  • DOI: 10.1038/nature14287

Coot model-building tools for molecular graphics
journal, November 2004

  • Emsley, Paul; Cowtan, Kevin
  • Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132
  • DOI: 10.1107/S0907444904019158

Role of c5a in Inflammatory Responses
journal, April 2005

C5a and pain development: An old molecule, a new target
journal, October 2016

Crystal structure of the β2 adrenergic receptor–Gs protein complex
journal, July 2011

  • Rasmussen, Søren G. F.; DeVree, Brian T.; Zou, Yaozhong
  • Nature, Vol. 477, Issue 7366
  • DOI: 10.1038/nature10361

Randomized Trial of C5a Receptor Inhibitor Avacopan in ANCA-Associated Vasculitis
journal, April 2017

  • Jayne, David R. W.; Bruchfeld, Annette N.; Harper, Lorraine
  • Journal of the American Society of Nephrology, Vol. 28, Issue 9
  • DOI: 10.1681/ASN.2016111179

Complement drives glucosylceramide accumulation and tissue inflammation in Gaucher disease
journal, February 2017

  • Pandey, Manoj K.; Burrow, Thomas A.; Rani, Reena
  • Nature, Vol. 543, Issue 7643
  • DOI: 10.1038/nature21368

Conserved waters mediate structural and functional activation of family A (rhodopsin-like) G protein-coupled receptors
journal, May 2009

  • Angel, T. E.; Chance, M. R.; Palczewski, K.
  • Proceedings of the National Academy of Sciences, Vol. 106, Issue 21
  • DOI: 10.1073/pnas.0903545106

Effective Application of Bicelles for Conformational Analysis of G Protein-Coupled Receptors by Hydrogen/Deuterium Exchange Mass Spectrometry
journal, March 2015

  • Duc, Nguyen Minh; Du, Yang; Thorsen, Thor S.
  • Journal of The American Society for Mass Spectrometry, Vol. 26, Issue 5
  • DOI: 10.1007/s13361-015-1083-4

PHENIX: a comprehensive Python-based system for macromolecular structure solution
journal, January 2010

  • Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
  • Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221
  • DOI: 10.1107/S0907444909052925

Low-Molecular-Weight Peptidic and Cyclic Antagonists of the Receptor for the Complement Factor C5a
journal, June 1999

  • Finch, Angela M.; Wong, Allan K.; Paczkowski, Natalii J.
  • Journal of Medicinal Chemistry, Vol. 42, Issue 11
  • DOI: 10.1021/jm9806594

Mapping the Ligand-Binding Site on the C5a Receptor:  Arginine 74 of C5a Contacts Aspartate 282 of the C5a Receptor
journal, November 2001

  • Cain, Stuart A.; Coughlan, Teresa; Monk, Peter N.
  • Biochemistry, Vol. 40, Issue 46
  • DOI: 10.1021/bi011055w

Rapid Context-Dependent Ligand Desolvation in Molecular Docking
journal, August 2010

  • Mysinger, Michael M.; Shoichet, Brian K.
  • Journal of Chemical Information and Modeling, Vol. 50, Issue 9
  • DOI: 10.1021/ci100214a

Molecular control of δ-opioid receptor signalling
journal, January 2014

  • Fenalti, Gustavo; Giguere, Patrick M.; Katritch, Vsevolod
  • Nature, Vol. 506, Issue 7487
  • DOI: 10.1038/nature12944

journal, May 1999

  • Baranski, Thomas J.; Herzmark, Paul; Lichtarge, Olivier
  • Journal of Biological Chemistry, Vol. 274, Issue 22
  • DOI: 10.1074/jbc.274.22.15757

Biologically Active Conformer of the Effector Region of Human C5a and Modulatory Effects of N-Terminal Receptor Binding Determinants on Activity
journal, March 1997

  • Finch, Angela M.; Vogen, Shawn M.; Sherman, Simon A.
  • Journal of Medicinal Chemistry, Vol. 40, Issue 6
  • DOI: 10.1021/jm960727r

Recent developments in low molecular weight complement inhibitors
journal, December 2009

Structural insights into µ-opioid receptor activation
journal, August 2015

  • Huang, Weijiao; Manglik, Aashish; Venkatakrishnan, A. J.
  • Nature, Vol. 524, Issue 7565
  • DOI: 10.1038/nature14886

Identification and Characterization of NDT 9513727 [ N , N -bis(1,3-Benzodioxol-5-ylmethyl)-1-butyl-2,4-diphenyl-1 H -imidazole-5-methanamine], a Novel, Orally Bioavailable C5a Receptor Inverse Agonist
journal, August 2008

  • Brodbeck, Robbin M.; Cortright, Daniel N.; Kieltyka, Andrzej P.
  • Journal of Pharmacology and Experimental Therapeutics, Vol. 327, Issue 3
  • DOI: 10.1124/jpet.108.141572

Enhancement of Human Cancer Cell Motility and Invasiveness by Anaphylatoxin C5a via Aberrantly Expressed C5a Receptor (CD88)
journal, January 2013

Modeling Molecular Mechanisms of Binding of the Anaphylatoxin C5a to the C5a Receptor
journal, March 2008

  • Nikiforovich, Gregory V.; Marshall, Garland R.; Baranski, Thomas J.
  • Biochemistry, Vol. 47, Issue 10
  • DOI: 10.1021/bi702321a

Identification of Phosphorylation Codes for Arrestin Recruitment by G Protein-Coupled Receptors
journal, July 2017

C5L2: a controversial receptor of complement anaphylatoxin, C5a
journal, March 2013

  • Li, Rui; Coulthard, Liam G.; Wu, M. C. L.
  • The FASEB Journal, Vol. 27, Issue 3
  • DOI: 10.1096/fj.12-220509

journal, June 2003

  • Klco, Jeffery M.; Lassere, Tracey B.; Baranski, Thomas J.
  • Journal of Biological Chemistry, Vol. 278, Issue 37
  • DOI: 10.1074/jbc.M305606200

Immunological effects and therapeutic role of C5a in cancer
journal, November 2014

  • Darling, Victoria R.; Hauke, Ralph J.; Tarantolo, Stefano
  • Expert Review of Clinical Immunology, Vol. 11, Issue 2
  • DOI: 10.1586/1744666X.2015.983081

Phaser crystallographic software
journal, July 2007

  • McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D.
  • Journal of Applied Crystallography, Vol. 40, Issue 4
  • DOI: 10.1107/S0021889807021206