Geoffrey Chang

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Geoffrey Chang is an associate professor at The Scripps Research Institute in La Jolla, California, United States. His laboratory focuses on the structural biology of integral membrane proteins, particularly exploring X-ray crystallography techniques for solving the tertiary structures of membrane proteins that are notoriously resistant to crystallization. The laboratory has specialized in structures of multidrug resistance transporter proteins in bacteria. In 2001, Chang was awarded a Beckman Foundation Young Investigator Award, designed to support researchers early in their academic careers, for his work on the structural biology of multidrug resistance.[1]

Chang and coauthors have published five papers on the structures of two multidrug resistance transporters, known as EmrE and MsbA, between 2001 and 2006. Although the initial structures were widely considered puzzling in the field due to their unexpected placement of their ATP binding sites in the assembled dimer,[2] the publication of an additional structure in the same protein family indicated that the Chang structures were unlikely to represent the biologically active conformation of the molecules.[3] Chang and coauthors are currently issuing retractions of their five structural papers on EmrE and MsbA, citing an error in an internal software utility as the source of the data misinterpretation that led to the appearance of wrongly assembled dimers.[4][5] The application of a popular protein structure validation tool to one of the retracted MsbA structures results in scores that indicate severe errors in this structure.[6]

Retracted papers

The following three papers in the journal Science have been retracted:[4]

  • Chang G, Roth CB. (2001) Structure of MsbA from E. coli: a homolog of the multidrug resistance ATP binding cassette (ABC) transporters. Science 293(5536):1793-800. PMID 11546864
  • Pornillos O, Chen YJ, Chen AP, Chang G. (2005) X-ray structure of the EmrE multidrug transporter in complex with a substrate. Science 310(5756):1950-3. PMID 16373573
  • Reyes CL, Chang G. (2005) Structure of the ABC transporter MsbA in complex with ADP.vanadate and lipopolysaccharide. Science 308(5724):1028-31. PMID 15890884

These two papers on the same subject will be retracted in upcoming issues of their journals.[7]

  • Chang G. (2003). Structure of MsbA from Vibrio cholera: a multidrug resistance ABC transporter homolog in a closed conformation. J Mol Biol 330(2):419-30. PMID 12823979
  • Ma C, Chang G. (2004). Structure of the multidrug resistance efflux transporter EmrE from Escherichia coli. Proc Natl Acad Sci USA 101(9):2852-7. PMID 14970332

References

  1. The Scripps Research Institute News and Views. In Brief 1(9): 2 Apr 2001. Access date 17 Jan 2001.
  2. Higgins CF, Linton KJ. (2001). Structural biology. The xyz of ABC transporters. Science 293(5536):1782-4. PMID 11546861
  3. Dawson RJ, Locher KP. (2006). Structure of a bacterial multidrug ABC transporter. Nature 443(7108):180-5. PMID 16943773
  4. 4.0 4.1 Chang G, Roth CB, Reyes CL, Pornillos O, Chen YJ, Chen AP. (2006). Retraction. Science 314(5807):1875 PMID 17185584
  5. Miller G. (2006). Scientific publishing. A scientist's nightmare: software problem leads to five retractions. Science 314(5807):1856-7. PMID 17185570
  6. Wiederstein M, Sippl MJ. (2007). ProSA-web: interactive web service for the recognition of errors in three-dimensional structures of proteins. Nucleic Acids Res, doi: 10.1093/nar/gkm290. PMID 17517781
  7. Gawrylewski A. (2006). Retractions unsettle structural bio: Recent findings upend conclusions from five highly-cited papers The Scientist 4 Jan 2007 Free full text Access date 17 Jan 2007.

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