N-terminal structure

The results concerning the N-terminal structures of glycophorins A" and A were based on the labels that were placed on the crucial, N-terminal amino group, and they clearly showed that the amino acid residues at position S may play only a minor, if any, role in determining the structure of the MN blood-group determinants. The carbohydrate residues appear... 

In the 1970s, Hughes et al. were the first to show that two very different chemical structures have similar agonist properties (3). The opioid natural product, morphine (3), was found to resemble the N-terminal structure of the endogenous opioid peptides, enkephalins, (4a) and (4b), and j3-endorphin (5) (Fig. 15.2). The remarkable similarity between the morphine phenol system and the IV-terminal tyrosine residue in the peptide opioids implied that these units reacted with opioid receptors in a similar fashion to elicit comparable responses (4-6). 

J.C., et al. (1993) Rationally designed dipeptoid analogues of cholecystokinin (CCK) N-terminal structure-affinity relationships of a-methyltryptophan derivatives. Eur. J. Med. Chem. 28 37-45. 

N-terminal structural modifications on antagonist potency were investigated (84)- First, the amino group of Phe was removed... 

Evidence for a Distinctive N-Terminal Structure of the Microsomal but Not the Peroxisomal Enzyme... 

It can be seen from Table 2 that the intrinsic values of the pK s are close to the model compound value that we use for Cys(8.3), and that interactions with surrounding titratable residues are responsible for the final apparent values of the ionization constants. It can also be seen that the best agreement with the experimental value is obtained for the YPT structure suplemented with the 27 N-terminal amino acids, although both the original YPT structure and the one with the crystal water molecule give values close to the experimentally determined one. Minimization, however, makes the agreement worse, probably because it w s done without the presence of any solvent molecules, which are important for the residues on the surface of the protein. For the YTS structure, which refers to the protein crystallized with an SO4 ion, the results with and without the ion included in the calculations, arc far from the experimental value. This may indicate that con-... 

Only the N terminal amide bond is broken m the Edman degradation the rest of the peptide chain remains intact It can be isolated and subjected to a second Edman procedure to determine its new N terminus We can proceed along a peptide chain by beginning with the N terminus and determining each ammo acid m order The sequence is given directly by the structure of the PTH derivative formed m each successive degradation... 

Figure S.7 The subunit structure of the neuraminidase headpiece (residues 84-469) from influenza virus is built up from six similar, consecutive motifs of four up-and-down antiparallel fi strands (Figure 5.6). Each such motif has been called a propeller blade and the whole subunit stmcture a six-blade propeller. The motifs are connected by loop regions from p strand 4 in one motif to p strand 1 in the next motif. The schematic diagram (a) is viewed down an approximate sixfold axis that relates the centers of the motifs. Four such six-blade propeller subunits are present in each complete neuraminidase molecule (see Figure 5.8). In the topological diagram (b) the yellow loop that connects the N-terminal P strand to the first P strand of motif 1 is not to scale. In the folded structure it is about the same length as the other loops that connect the motifs. (Adapted from J. Varghese et al.. Nature 303 35-40, 1983.)...

Figure 6.8 Schematic diagram of the enzyme DsbA which catalyzes disulfide bond formation and rearrangement. The enzyme is folded into two domains, one domain comprising five a helices (green) and a second domain which has a structure similar to the disulfide-containing redox protein thioredoxin (violet). The N-terminal extension (blue) is not present in thioredoxin. (Adapted from J.L. Martin et al.. Nature 365 464-468, 1993.)...

Figure 6.20 Space-filling diagram illustrating the structural changes of CDK2 upon cyclin binding, (a) The active site is in a cleft between the N-terminal domain (blue) and the C-terminal domain (purple). In the inactive form this site is blocked by the T-loop.

Figure 6.23 Schematic diagram illustrating the active site loop regions (red) in three forms of the serpins. (a) In the active form the loop protrudes from the main part of the molecuie poised to interact with the active site of a serine proteinase. The first few residues of the ioop form a short p strand inserted between ps and pis of sheet A. (h) As a result of inhibiting proteases, the serpin molecules are cleaved at the tip of the active site ioop region, in the cleaved form the N-terminal part of the loop inserts itself between p strands 5 and 15 and forms a long p strand (red) in the middie of the p sheet, (c) In the most stable form, the latent form, which is inactive, the N-terminai part of the ioop forms an inserted p strand as in the cleaved form and the remaining residues form a ioop at the other end of the p sheet. (Adapted from R.W. Carreii et ai., Structure 2 257-270, 1994.)...

Figure 8.6 The N-terminal domain of lambda repressor, which binds DNA, contains 92 amino acid residues folded into five a helices. Two of these, a2 (blue) and a3 (red) form a helix-turn-hellx motif with a very similar structure to that of lambda Cro shown In Figure 8.4. The complete repressor monomer contains in addition a larger C-termlnal domain. (Adapted from C. Pabo and M. Lewis, Nature 298 443-447, 1982.)...

The x-ray structure of the N-terminal DNA-binding domain of the lambda repressor was determined to 3.2 A resolution in 1982 by Carl Pabo at Harvard University and revealed a structure with striking similarities to that of Cro, although the p strands in Cro are replaced by a helices in repressor. 

The polypeptide chain of the 92 N-terminal residues is folded into five a helices connected by loop regions (Figure 8.6). Again the helices are not packed against each other in the usual way for a-helical structures. Instead, a helices 2 and 3, residues 33-52, form a helix-turn-helix motif with a very similar structure to that found in Cro. 

The 434 Cro molecule contains 71 amino acid residues that show 48% sequence identity to the 69 residues that form the N-terminal DNA-binding domain of 434 repressor. It is not surprising, therefore, that their three-dimensional structures are very similar (Figure 8.11). The main difference lies in two extra amino acids at the N-terminus of the Cro molecule. These are not involved in the function of Cro. By choosing the 434 Cro and repressor molecules for his studies, Harrison eliminated the possibility that any gross structural difference of these two molecules can account for their different DNA-binding properties. 

The polypeptide chain of the lac repressor subunit is arranged in four domains (Figure 8.21) an N-terminal DNA-hinding domain with a helix-turn-helix motif, a hinge helix which binds to the minor groove of DNA, a large core domain which binds the corepressor and has a structure very similar to the periplasmic arablnose-binding protein described in Chapter 4, and finally a C-terminal a helix which is involved in tetramerization. This a helix is absent in the PurR subunit structure otherwise their structures are very similar. 

Many biochemical and biophysical studies of CAP-DNA complexes in solution have demonstrated that CAP induces a sharp bend in DNA upon binding. This was confirmed when the group of Thomas Steitz at Yale University determined the crystal structure of cyclic AMP-DNA complex to 3 A resolution. The CAP molecule comprises two identical polypeptide chains of 209 amino acid residues (Figure 8.24). Each chain is folded into two domains that have separate functions (Figure 8.24b). The larger N-terminal domain binds the allosteric effector molecule, cyclic AMP, and provides all the subunit interactions that form the dimer. The C-terminal domain contains the helix-tum-helix motif that binds DNA. 

The 12 residues between the second cysteine zinc ligand and the first histidine ligand of the classic zinc finger motif form the "finger region". Structurally, this region comprises the second p strand, the N-terminal half of the helix and the two residues that form the turn between the p strand and the helix. This is the region of the polypeptide chain that forms the main interaction area with DNA and these interactions are both sequence specific. 

Figure 11.13 Schematic diagram of the three-dimensional structure of subtilisin viewed down the central parallel p sheet. The N-terminal region that contains the a/p stmcture is blue.

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