E-Newsletter
July 2010 E-Newsletter
DEAR COLLEAGUES
Welcome to Emerald BioStructures' new e-Newsletter. For 12 years, we've given our clients the advantage of greater insight into their drug discovery programs. Recent innovations allow us to now offer low-cost, fast turn-around targets through a new program called CrystalReady™. Our expanded services and capabilities in Gene-to-Structure and Fragment Screening can help get your leads to clinic faster.
Whether you're a current client, a former one, or simply interested in our latest developments, read on. To accelerate your leads-development program, call us today at 206-780-8959.
Lance Stewart, CEO
COLLABORATIONS
Through our world-class X-ray crystallography and structure-based design capabilities, we provide our clients with the advantage of structural insight into target-ligand binding models. We characterize protein-ligand interactions using all major assay and biophysical screening techniques (X-ray, NMR, SPR, ITC, and others). Our Fragments of Life™ technology for fragment based drug discovery has produced leads for a wide variety of targets.
Recent collaboration news includes:
- UCB: Emerald recently announced a significant milestone achievement in our ongoing collaboration with UCB by obtaining multiple high resolution X-ray crystallographic structures of small fragment-like molecules that antagonize inflammatory cytokine signaling. This success demonstrates Emerald's ability to collaborate on difficult targets including discovery of allosteric small molecules that modulate protein structure.
- FORMA Therapeutics: Following delivery of multiple kinase ligand bound structures, Emerald initiated a multi-year gene-to-structure research collaboration with FORMA to obtain a large number of ligand-bound structures against a diverse set of cancer targets. This collaboration leverages Emerald's high throughput structural biology platform.
- Cystic Fibrosis Foundation Therapeutics: Emerald recently announced the initiation of a new research collaboration with CFFT to perform crystallization and crystallographic screening experiments against the CFTR (Cystic Fibrosis Transmembrane conductance Regulator) using Emerald's Fragments of Life™ library. The research collaboration provides Cystic Fibrosis Foundation Therapeutics access to Emerald's advanced membrane protein crystallization platform and Emerald's expertise for difficult protein targets.
CORPORATE UPDATES
Infrastructure Improvements
We expanded our laboratory facilities with the addition of new NMR instrumentation and automated plate imaging hotel systems with improved crystallization management software. We also set up an innovative Matrix Maker clean room at our sister company Emerald BioSystems which supports on-demand eWizard crystallization screen production from over 240 stock chemicals.
200th Structure Solved
Emerald recently solved the 200th novel infectious disease protein crystal structure within the Seattle Structural Genomics Center for Infectious Disease (SSGCID), a large collaboration with our colleagues at Seattle BioMed, the University of Washington, and Battelle Memorial Institute / Pacific Northwest National Laboratory. We are now solving 100+ crystal structures of novel infectious disease protein targets each year in this 5-year project, including several fragment and ligand bound target structures. SSGCID has already become one of the world's most productive structural genomics projects.
Innovative Protein Structure Technologies
Emerald has successfully completed the Accelerated Technologies Center for Gene to 3D Structure (ATCG3D ) project. ATCG3D was a 5-year Specialized Technology Center funded by the NIH as part of the Protein Structure Initiative which resulted in the development of three new enabling technologies:
- Our Microcapillary Protein Crystallization System (MPCS Plug Maker) won a prestigious ALA New Product Award at the January 2010 Lab Automation Meeting. The MPCS Plug Maker and CrystalCards enable crystallization in 20nl plugs with chips that can be easily peeled apart to harvest and mount crystals. These products are available from our sister company Emerald BioSystems. Call 206-780-8535 for a demo today. The MPCS technology evolved out of the laboratory of Dr. Rustem Ismagilov at the University of Chicago and was the subject of a recent technology transfer highlight from UChicagoTech News. We are now growing and storing crystals in a "bank" of CrystalCards which is greatly facilitating our Crystal Ready business.
- Gene Composer™ software for structure-guided construct and codon engineering is available for free 1-year trial download.
- Compact Light Source at Lyncean Technologies, a novel inverse Compton X-ray source was invented by Dr. Ron Ruth and colleagues at Lyncean. Emerald recently published a paper on the first novel protein X-ray crystal structure to be solved from data collected using the Compact Light Source.
New Management Team Member
Please join us in welcoming Dr. Diana Wetmore, who has joined Emerald BioStructures as our Vice President of Business Development and Alliances. Diana was formerly at the Cystic Fibrosis Foundation in a similar role. Her prior business development successes, together with 10 years of scientific accomplishments in Industry, make her an ideal fit as we continue to pursue partnerships with organizations that need help solving their important drug discovery challenges.
2010 PUBLICATIONS
The work of Emerald scientists has recently been published in several high-impact journals.
Our work on the structure guided design of a novel class of allosteric modulators of phosphodiesterase 4D was the cover story in the January 2010 issue of Nature Biotechnology.
Design of phosphodiesterase 4D (PDE4D) allosteric modulators for enhancing cognition with improved safety.
Burgin AB, Magnusson OT, Singh J, Witte P, Staker BL, Bjornsson JM, Thorsteinsdottir M, Hrafnsdottir S, Hagen T, Kiselyov AS, Stewart LJ, Gurney ME.
Nat Biotechnol. 2010 Jan;28(1):63-70. PubMed PMID: 20037581.
We produced novel synthetic 3'-bridging phosphothiolate oligonucleotide substrates that aided the structural elucidation of a novel catalytic mechanism for topoisomerase II.
A novel and unified two-metal mechanism for DNA cleavage by type II and IA topoisomerases.
Schmidt BH, Burgin AB, Deweese JE, Osheroff N, Berger JM.
Nature. 2010 Jun 3;465(7298):641-4. PubMed PMID: 20485342.
Emerald scientist Tom Edwards solved a series of crystal structures of the thiamine pyrophosphate riboswitch, which were followed here by another structure and extensive biochemical and biophysical characterization of the ligand specificity of this mRNA genetic control element.
Thermodynamic analysis of ligand binding and ligand binding-induced tertiary structure formation by the thiamine pyrophosphate riboswitch.
Kulshina N, Edwards TE, Ferré-D'Amaré AR.
RNA. 2010 Jan;16(1):186-96.
Epub 2009 Nov 30. PubMed PMID: 19948769; PubMed Central PMCID: PMC2802028.
In a collaborative SSGCID effort, the structure of adenylate kinase from Burkholderia pseudomallei was solved by Se-Met SAD phasing. The two conformations of the protein observed in the crystal structures might correspond to the open and the closed state of this highly mobile protein.
Structural characterization of Burkholderia pseudomallei adenylate kinase (Adk): profound asymmetry in the crystal structure of the 'open' state.
Buchko GW, Robinson H, Abendroth J, Staker BL, Myler PJ.
Biochem Biophys Res Commun. 2010 Apr 16;394(4):1012-7. Epub 2010 Mar 21. PubMed PMID: 20331978; PubMed Central PMCID: PMC2856777.
Our collaborative work with Tibotec led to structural insights into the mode of action for inhibitors of Respiratory Syncytial Virus replication.
Binding of a potent small-molecule inhibitor of six-helix bundle formation requires interactions with both heptad-repeats of the RSV fusion protein.
Roymans D, De Bondt HL, Arnoult E, Geluykens P, Gevers T, Van Ginderen M, Verheyen N, Kim H, Willebrords R, Bonfanti JF, Bruinzeel W, Cummings MD, van Vlijmen H, Andries K.
Proc Natl Acad Sci U S A. 2010 Jan 5;107(1):308-13. Epub 2009 Dec 4.PMID: 19966279
A collaborative effort between our SSGCID and ATCG3D projects led to the first novel X-ray crystal structure determination from a novel Compact Light Source.
X-ray structure determination of the glycine cleavage system protein H of Mycobacterium tuberculosis using an inverse Compton synchrotron X-ray source.
Abendroth J, McCormick MS, Edwards TE, Staker B, Loewen R, Gifford M, Rifkin J, Mayer C, Guo W, Zhang Y, Myler P, Kelley A, Analau E, Hewitt SN, Napuli AJ, Kuhn P, Ruth RD, Stewart LJ.
J Struct Funct Genomics. 2010 Mar;11(1):91-100. Epub 2010 Apr 3.
UPCOMING EVENTS
Connect with Emerald scientists at the following events:
American Crystallographic Association 2010 Annual Meeting
Chicago, IL
July 24-29, 2010
2010 Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC)
Boston, MA
September 12-15, 2010
18th Annual BioPartnering Europe
London, United Kingdom
October 10-12, 2010
Fragment-based Lead Discovery Conference 2010
Philadelphia, PA
October 10-13, 2010
Advances in Protein Crystallography
Florence, Italy
November 9-10, 2010
Protein Structure Determination in Industry 2010
Oxford, United Kingdom
November 15-16, 2010
BioEurope 2010
Munich, Germany
November 15-17, 2010
CONTACT US
Diana R. Wetmore, Ph.D.
Vice President of Business Development and Alliances
dwetmore@embios.com
206-780-8959
©2010 Emerald BioStructures. All rights reserved. CrystalReady, Fragments of Life, and Gene Composer are trademarks of Emerald BioStructures. Other trademarks are property of their respective owners.