Clarifying allosteric control of flap conformations in the 1TW7 crystal structure of HIV-1 protease This work was performed at the University of Michigan, Ann Arbor, MI.
dc.contributor.author | Lexa, Katrina Walden | en_US |
dc.contributor.author | Damm, Kelly Lynn | en_US |
dc.contributor.author | Quintero, Jerome J. | en_US |
dc.contributor.author | Gestwicki, Jason E. | en_US |
dc.contributor.author | Carlson, Heather A. | en_US |
dc.date.accessioned | 2009-03-03T20:09:18Z | |
dc.date.available | 2010-04-14T17:40:05Z | en_US |
dc.date.issued | 2009-03 | en_US |
dc.identifier.citation | Lexa, Katrina W.; Damm, Kelly L.; Quintero, Jerome J.; Gestwicki, Jason E.; Carlson, Heather A. (2009). "Clarifying allosteric control of flap conformations in the 1TW7 crystal structure of HIV-1 protease This work was performed at the University of Michigan, Ann Arbor, MI. ." Proteins: Structure, Function, and Bioinformatics 74(4): 872-880. <http://hdl.handle.net/2027.42/61876> | en_US |
dc.identifier.issn | 0887-3585 | en_US |
dc.identifier.issn | 1097-0134 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/61876 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=18704936&dopt=citation | en_US |
dc.description.abstract | The 1TW7 crystal structure of HIV-1 protease shows the flaps placed wider and more open than what is seen in other examples of the semi-open, apo form. It has been proposed that this might be experimental evidence of allosteric control, because crystal packing creates contacts to the “elbow region” of the protease, which may cause deformation of the flaps. Recent dynamics simulations have shown that the conformation seen in 1TW7 relaxes into the typical semi-open conformation in the absence of the crystal contacts, definitively showing that the crystal contacts cause the deformation (Layten et al. , J Am Chem Soc 2006;128:13360–13361). However, this does not prove or disprove allosteric modulation at the elbow. In this study, we have conducted additional simulations, supplemented with experimental testing, to further probe the possibility of 1TW7 providing an example of allosteric control of the flap region. We show that the contacts are unstable and do not restrict the conformational sampling of the flaps. The deformation seen in the 1TW7 crystal structure is simply opportunistic crystal packing and not allosteric control. Proteins 2009. © 2008 Wiley-Liss, Inc. | en_US |
dc.format.extent | 597503 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.publisher | Wiley Subscription Services, Inc., A Wiley Company | en_US |
dc.subject.other | Chemistry | en_US |
dc.subject.other | Biochemistry and Biotechnology | en_US |
dc.title | Clarifying allosteric control of flap conformations in the 1TW7 crystal structure of HIV-1 protease This work was performed at the University of Michigan, Ann Arbor, MI. | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Biological Chemistry | en_US |
dc.subject.hlbtoplevel | Science | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Department of Medicinal Chemistry, University of Michigan, Ann Arbor, Michigan 48109-1065 | en_US |
dc.contributor.affiliationum | Department of Medicinal Chemistry, University of Michigan, Ann Arbor, Michigan 48109-1065 | en_US |
dc.contributor.affiliationum | Biophysics Research Division, University of Michigan, Ann Arbor, Michigan 48109-1055 | en_US |
dc.contributor.affiliationum | Life Sciences Institute and Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109-2216 | en_US |
dc.contributor.affiliationum | Department of Medicinal Chemistry, University of Michigan, Ann Arbor, Michigan 48109-1065 ; Biophysics Research Division, University of Michigan, Ann Arbor, Michigan 48109-1055 ; The University of Michigan, College of Pharmacy, 428 Church St., Ann Arbor, MI 48109-1065 | en_US |
dc.identifier.pmid | 18704936 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/61876/1/22195_ftp.pdf | |
dc.identifier.doi | 10.1002/prot.22195 | en_US |
dc.identifier.source | "Proteins: Structure, Function, and Bioinformatics" | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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