title: Allosteric intermediates indicate R2 is the liganded hemoglobin end state.
abstract: Hemoglobin has been a long-standing paradigm for understanding protein allostery. Here, the x-ray structures of two chemically crosslinked, fully liganded hemoglobins, alpha2beta82CA82beta and alpha2beta82ND82beta, are described at 2.3 A and 2.6 A resolution, respectively. Strikingly, these crosslinked hemoglobins assume intermediate conformations that lie between those of R and the controversial liganded hemoglobin state R2 rather than between R and T. Thus, these structures support only a T left and right arrow R left and right arrow R2 allosteric pathway and underscore the physiological importance of the R2 conformation.
authors.affiliation: Department of Biochemistry and Molecular Biology, Oregon Health Sciences University, 3181 SW Sam Jackson Park Road, Portland, OR 97201-3098, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Schumacher
authors.forename: E E
authors.initials: EE
authors.lastname: Zheleznova
authors.forename: K S
authors.initials: KS
authors.lastname: Poundstone
authors.forename: R
authors.initials: R
authors.lastname: Kluger
authors.forename: R T
authors.initials: RT
authors.lastname: Jones
authors.forename: R G
authors.initials: RG
authors.lastname: Brennan
mesh_terms: D000494:Allosteric Regulation; D006454:Hemoglobins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D011487:Protein Conformation
chemical_list: D006454:Hemoglobins; D008024:Ligands