Tensed state

Reactivity. Hemoglobin can exist ia either of two stmctural coaformatioas, corresponding to the oxy (R, relaxed) or deoxy (T, tense) states. The key differences between these two stmctures are that the constrained T state has a much lower oxygen affinity than the R state and the T state has a lower tendency to dissociate into subunits that can be filtered in the kidneys. Therefore, stabilization of the T conformation would be expected to solve both the oxygen affinity and renal excretion problems. 

The interactions between the allosteric effectors and hemoglobin add hydrogen bonds to the Hb tense state, similar to DPG, and therefore stabilize that state, resulting in an increased delivery of oxygen. 

While occupancy theory is far and away the most widely used model for describing dose-response curves, other theories do exist. One example is allosteric theory. At the center of allosteric theory, sometimes called the two-state model, is the idea that a receptor can exist in conformations that either cause a response (relaxed state) or do not cause a response (tensed state).29 These conformations, represented by T and R, are in equilibrium (Scheme 5.7). 

In contrast, Monod, Wyman, and Changeux proposed a simple model, which is called the MWC two-state concerted model. They defined two quaternary T and R states the T (tense) state exhibits low affinity whereas the R (relaxed) state exhibits high affinity. This model assumes that each... 

The quaternary structure observed m the deoxy form of hemoglobin is often referred to as the T (for tense) state because it is quite constrained by subunit—subunit interactions. The quaternary structure of the fully oxygenated form is referred to as the R (for relaxed) state. In light of the observation that the R form of hemoglobin is less constrained, the tense and relaxed designations seem particularly apt. Importantly, in the R state, the... 

The mammalian (largely rabbit) muscle enzyme has been the most investigated X-ray structural work favours a GTB fold. It has control, covalent and allosteric, at several levels and these are usually discussed in terms of a modification of the Monod-Wyman-Changeux model, in which the individual polypeptide monomers can adopt either a non-catalytic T ( tense ) state or a catalytic R ( relaxed ) state, but mixed oligomers (e.g. TR in a dimer) do not occur. In the extensive structural studies, oligomers with mixed conformations have never been observed. 

The structural difference between the active GTP-state and the inactive GDP-state of the Ras protein is primarily confined to the switch I and switch II regions. The conformational change can be described best by a loaded spring mechanism (see Fig. 5.22), where the two switch regions are fixed by the y-phosphate of GTP in a tense state. Upon GTP-hydrolysis, the two switch regions are allowed to relax into the GDP-spe-cific position. Thereby, the coordination of switch I to the y-phosphate and to Mg2 is lost as well as the interaction of the conserved Gly60 in switch II with the y-phosphate. 

Fig. 6. ATPase-coupled N-terminal dimerization in Hsp90. BindingofATPtoan Hsp90 dimer promotes association of the N-terminal nucleotide-binding domains into a tense state, which in turn promotes ATP hydrolysis. The ADP thus generated does not favor N-terminal association and allows relaxation into the relaxed state, completing the cycle (From Prodromou et al, 2000, with permission).

Case study Refinement of a partially oxygenated T (tense) state human haemoglobin (Hb) at 1.5 A resolution (Waller and... 

Fig. 18. Schematic representation of the a-cyclodextrin - substrate inclusion process. The empty a-cyclodextrin molecule in the upper left hand corner corresponds to the a-cyclodextrin (H20)2 complex found in the crystal structure [12, 13]. Only four of the six 0(2) 0(3) interglucosidic hydrogen bonds are formed and the molecule is in a tense state with high conformational and low hydrogen bonding energy. Upon adduct formation via routes A, B or C it goes into a relaxed , com-plexed state with all 0(2) 0(3) hydrogen bonds formed and with low conformational energy.

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