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Frauenfelder, Hans Philipp, Robert Georg 2011-04-26T15:35:21Z 2011-04-26T15:35:21Z 10000-01-01 1994-05 Myoglobin and hemoglobin are dioxygen storage and transport proteins. They bind small molecules (ligands) such as dioxygen (02) and carbon monoxide (CO) reversibly. The active site is the heme, a disc shaped molecule which sits in a pocket of the protein (heme pocket). At the center of the heme is an iron (Fe) atom, to which the ligands bind reversibly when the Fe is in the ferrous state. The ligand binding rates of these proteins depend on the type of ligand. For example, myoglobin and hemoglobin bind 02 faster, but with lower affinity, than they bind CO. The mechanism with which these proteins control ligand binding is not fully known, and remains a fundamental issue, if the general principles of ligand binding are to be understood. Protein motions are essential for myoglobin and hemoglobin to perform their function. X-ray crystal structures show no pathways through which the ligands can enter and exit the protein. Without the ability of ligand entry and exit, myoglobin and hemoglobin could not deliver 02 to the required tissues. Large scale motions are required to open pathways for ligand entry and exit. Additional motions have been shown to be important for control of the ligand binding barrier. The bound and deoxy structures of myoglobin and hemoglobin are different, respectively. One important difference is the position of the heme-iron relative to the heme plane. Upon ligand dissociation, the Fe relaxes to its unbound position. Movement of the Fe out of the mean heme-plane has been correlated to the height of the rebinding enthalpy barrier. We have conducted flash photolysis experiments on R and T state carp hemoglobin and sperm whale myoglobin over a wide range in temperature (lOK to 300K) and time (30ns to lOOs). Our data show that the conformational relaxation of the Fe out-of-plane distance proceeds in discrete steps which can be correlated with peaks in the rebinding lifetime distribution, j(logt). In addition we show that this conformational relaxation can be enhanced through photons absorbed by the heme. A model is presented in which the ligand must wait for a conformational rearrangement of the Fe, to the approximate bound position, before bond formation can occur. This conformational rearrangement is controlled on the proximal side (opposite side to the ligand binding site) of the heme. The consequences of this model on the binding of 02 by myoglobin are discussed. Many of the features of 02 rebinding are predicted by this model, and the model suggests a mechanism by which these proteins discriminate between CO and 02. Additional research on the binding of 02 must be performed. Submitted by Carolyn Mead (cmead2@illinois.edu) on 2011-04-26T15:35:21Z No. of bitstreams: 1 1994_philipp.pdf: 4402544 bytes, checksum: d7368053eefd609c6881ae7785952e2f (MD5) Made available in DSpace on 2011-04-26T15:35:21Z (GMT). No. of bitstreams: 1 1994_philipp.pdf: 4402544 bytes, checksum: d7368053eefd609c6881ae7785952e2f (MD5) Previous issue date: 1994-05 Restriction data tranferred 2014-07-01T11:12:11-05:00 Original Data Group with Access UIUC Users [automated] Release Date: none Reason: Thesis Item marked as restricted to the 'UIUC Users [automated]' Group (id=2) by Carolyn Mead (cmead2@illinois.edu) on 2011-04-26T15:35:21Z Item is restricted indefinitely. Thesis U of I Only 3739537 http://hdl.handle.net/2142/18876 en 1994 Robert Georg Philipp myoglobin hemoglobin Biophysics ligand binding conformational motions The role of conformational motions in the control of ligand binding to myoglobin and hemoglobin Dissertation / Thesis text Physics Physics University of Illinois at Urbana-Champaign Dissertation Ph.D.