June 20, 2011 - IMM@BUCT

NEWS OF THE WEEKSTRUCTURE OFBRASSINOLIDE’SRECEPTOR SOLVEDAGRICULTURE : First look at sensorfor plant hormone holds surprisesTHE FIRST X-RAY crystal structures of a keyplant hormone receptor protein have beensolved by two independent research teamsworking in the U.S. and China ( Nature , DOI: 10.1038/nature10178 and 10.1038/nature10153). The receptorsenses brassinolide, a steroid that helps bulk up foliage,fight pathogens, and mediate fertilization. It is amongthe last of the major plant hormone receptors to haveits structure solved.The discovery sets the stage forplant researchers to improve theyields of lettuce and cotton, twocrops that depend on brassinolidesignaling for large harvests.The structure will also help plantscientists understand and bolsteragricultural crops’ immunity tomicrobial pathogens.Surprisingly, the brassinolidereceptor “looks totally differentthan what was expected,” saysPing He, a plant biochemist atHOHOTexas A&M University. People so strongly believed thereceptor would adopt a horseshoe shape, He explains,that the wrong structure was widely “put in textbooks.”Instead, the brassinolide receptor, called BRI1, adoptsa superhelix conformation that sequesters the hormoneHHHOHOBrassinolideinside the ring, with thehelp of an “island”domain, so namedbecause it appearsto float in the centerof the receptor’scircular interior.The two researchteams—one led bystructural biologistJijie Chai at Tsinghua University,in Beijing, and theother by Joanne Chory, a plantbiologist at the Salk Institute,in La Jolla, Calif.—knew of each other’swork, but did not share data prior to submittingthe papers for publication. When Chai finally readChory’s paper, “I could not find a difference betweentheir structure and ours,” he says. The impressive similarity“certainly helped” convinceOHHOHreviewers who were expecting BRI1to look like its mammalian analog,the horseshoe-shaped steroid receptorcalled TLR3, Chory says.The researchers were also surprisedto find that BRI1 does notseem to dimerize as TLR3 does,Chai says.Chemists could use BRI1’sstructure to develop small,receptor-activating molecules thataren’t as complicated—and thereforenot as expensive to produce orpurify—as brassinolide. The structure might also helpplant scientists engineer the receptor to increase cropsensitivity to brassinolide, thus speeding the launch ofdefensive strategies against invading microbial pests,He adds. —SARAH EVERTSThe proteinthat detects theplant hormonebrassinolideadopts anunexpectedsuperhelixconformation.NATUREPHARMACEUTICALS Merck deal with South Korea’s Hanwha bolsters move into biosimilarsMerck & Co. has agreed to pay SouthKorea’s Hanwha Chemical up to $720million for access to HD203, a biosimilarform of Amgen’s arthritis and psoriasistreatment Enbrel. The deal buttressesMerck’s ambition to become a leader inthe market for biosimilars, which are genericversions of biologic drugs.Last year, Enbrel logged $3.3 billion insales in the U.S., where it will lose patentprotection in October 2012.HD203 is in a Phase III study in Koreato confirm its safety and therapeuticequivalence to Enbrel in treating peoplewith rheumatoid arthritis. It has yet to besubject to clinical tests in the U.S.Merck will run additional clinical trialsfor and manufacture HD203, and it intendsto sell the drug in all countries outsideof Korea and Turkey, where Hanwharetains marketing rights. Hanwha willreceive an undisclosed up-front paymentfrom Merck, as well as milestonepayments. Hanwha could reap up to$720 million over the course of the pact,according to a financial filing from theSouth Korean firm.Merck has been working diligentlyto become a key player in the emergingbiosimilars marketplace since launchingMerck BioVentures, a unit dedicatedto developing generic biologics, in late2008. The company wants to havefive biosimilars in late-stage developmentin 2012, a goal that it hopes toachieve with the aid of partnerships andac qui si tions.The deal-making kicked off in 2006,with the acquisition of GlycoFi, a smallbiotech firm with technology to makeglycosylated proteins in yeast. In 2009,Merck licensed generic versions ofNe upogen and Neulasta, a pair of Amgenchemotherapy adjuncts, from Insmed.And earlier this year, Parexel agreed toprovide clinical development services forbiosimilar candidates being developedby Merck.—LISA JARVISWWW.CEN-ONLINE.ORG 13 JUNE 20, 2011