The dynamic picture derived from the present study provides new insights into the traditional description of the stereochemical mechanism for the cooperative oxygenation of Hb A based on X-ray crystallographic results. Several amino acid residues at the intradimer interfaces, such as beta109Val, appear to be involved in possible conformational exchange processes. Amino acid structure Amino acid C2H4-COOH: C3H6-N (in backbone).
POLYPEPTIDE BACKBONE SERIES
We have also found that there is considerable flexibility in the intradimer (alpha1beta1) interface (i.e., B, G, and H helices and the GH corner) and possible involvement of several amino acid residues (e.g., alpha31Arg, beta3Leu, beta41Phe, beta123Thr, and beta146His) in the allosteric pathway. Carboxylic acids (-COOH) exist at the C-terminus of each polypeptide chain and in the. The polypeptide backbone can thus be viewed as a series of planar 'plates' that can rotate relative to one another. Herein, we report a stereospecific E-olefin dipeptide isostere synthesis that can be used to make gram quantities of the PhePhe isostere desired for eliminating a specific backbone H-bond donor and acceptor in the Alzheimers disease related A peptide. These findings imply a role for alpha31Arg and beta123Thr in the intradimer communication but contradict the results from X-ray crystallography. While remarkably flexible in the deoxy state, alpha31Arg and beta123Thr, neighbors in the intradimer (alpha1beta1) interface, exhibit stiffening upon CO binding. We now have direct dynamics evidence for this structural transition of Hb in solution.
POLYPEPTIDE BACKBONE FREE
Although rigid in deoxy-Hb A, beta146His has been found to be free from restriction of its backbone motions in the CO form, presumably due to the rupture of its hydrogen bond/salt bridge network. This unnatural amino acid was genetically encoded in E. PTH is an 84-residue protein that controls key. In both deoxy and carbonmonoxy forms of human normal adult hemoglobin (Hb A), the amide N-H bonds of most amino acid residues are rigid on the fast time scale (nanosecond to picosecond), except for the loop regions and certain helix-helix connections. cleave the polypeptide backbone by an unusual cin- noline-forming reaction. We used PTHR1 signaling to evaluate a strategy for creating active and biostable backbone-modified analogs of the well-known agonist PTH (1-34). Model-free-based NMR dynamics studies have been undertaken for polypeptide backbone amide N-H bond vectors for both the deoxy and carbonmonoxy forms of chain-specific, isotopically (15N and 2H) labeled tetrameric hemoglobin (Hb) using 15N-relaxation parameters measured at two temperatures (29 and 34 degrees C) and two magnetic field strengths (11.7 and 14.1 T).
0 kommentar(er)
