Primary and three-dimensional structure

Fourteen complete transferrin and transferrin-related amino acid sequences have now 

On the basis of the following data, it is clear that transferrin evolution was highly conservative. 

---

Robinson N.E. and Robinson A.B. (2001), Prediction of protein deamidation rates from primary and three-dimensional structure, Proc. Nat. Acad. Sci. U.S.A. 98, 4367 1372. 

Matias PM, Coelho R, Pereira lA, et al. 1999. The primary and three-dimensional structures of a nine haem cytochrome c from Desulfovibrio desulfuricans ATCC 2111A reveal a new member of the Hmc family. Structure 7 119-30. 

Spik, G., Coddeville, B., Mazurier, J., Bourne, Y., Cambillaut, C., and Montreuil, J. 1994a. Primary and three-dimensional structure of lactotransferrin (lactoferrin) glycans. Adv. Exp. Med. Biol. 357, 21-32. 

Since the primary and three-dimensional structures of cytochrome c peroxidase are yet to be established, any discussion on its molecular... 

Overall, the loop between the /8 strands D and E is very conserved in both its primary and three-dimensional structure. Note the close conformational positioning of Phe-64 and Phe-70. If viewed in stereo, the two... 

Saether, O., Craik, D.J., Gampbell, I.D., Slet-ten, R., Juul, J., Norman, D.G. Elucidation of the primary and three-dimensional structure of the uterotonic polypeptide kalata Bl. Biochemistry 1995, 34, 4147-4158... 

G. Widmalm, A Perspective on the Primary and Three-Dimensional Structures of Carbohydrates, Carbohydr. Res., 2013, 378,123. 

In order to understand and explain the complex activities of a-LTX, its primary and three-dimensional (3D) structure has been thoroughly studied. 

The biological activity of proteins generally depends on a unique three-dimensional conformation, which in turn is inherently linked to its primary sequence. Protein folding, the conversion of the translated polypeptide chain into the native state of a protein, is the critical link between gene sequence and three-dimensional structure. Mechanistically, folding is believed to proceed through a predetermined and ordered pathway, either via kinetic intermediates or by direct transition from the unfolded to the native state [99]. In both cases, local and non-local interactions alike stabilize transient structures along the pathway and funnel the intermediates towards the native state. 

The X-ray crystal structures of MoFe protein, alone or in complex with the Fe protein, have been reported for A. vinelandii,C. pasteunanum, and K. pneumoniae, and all of these structures are highly conserved on the basis of both primary sequence and three-dimensional structure. The MoFe protein of A. vinelandii is an azPz heterotetramer consisting of a pair of ap dimers related by a molecular twofold rotation axis (Figure The homologous a and P subunits include three domains, designated al, all, and alll and pi, pH, and jSIII, respectively, all of which exhibit parallel /3-sheet/a-helical type of polypeptide folds. Domains of both subunits contribute ligands to the P cluster. These ligands are located in a common core of a four-stranded, parallel /3-sheet flanked by a-helices and additional /3-strands. The P clusters are located between... 

Primary hepatocytes or liver slices can be used to measure metabolism, but only for a short period of time after the liver sample has been removed from the body however, both models have problems associated with their use. In liver slices, cell-to-cell contact and three-dimensional structure are maintained with a full compliment of cell types (including Kupffer cells) primary hepatocytes have lost the orientation, organization, and nonhepatocyte cells which may contribute to the metabolic activity of the whole liver. Liver slices may suffer from the presence of damaged or dead cells, restricted access of culture media to internal cells, thereby reducing oxygen and nutrient supplies, and from a build-up of toxic products that may result in impaired metabolism. Perfusion of tissue in situ can ameliorate these problems, but of necessity such experiments can normally only be carried out in animals, and these will have different metabolic profiles due to differences in enzyme and transporter expression. 

Enzyme engineering arose only after advances in several other fields made it possible to determine the primary amino acid sequences and three-dimensional structure of enzymes and directly manipulate... 

Cytochrome C2 from Rhodospirillitan rubrum, a photosynthetic bacterium, is closely analogous in amino acid sequence and three dimensional structure to the soluble c-type cytochromes of eukaryotic species. X-ray crystallography studies have clearly established histidine and methionine as axial ligands to the heme group (Salemme et ai, 1973). Cytochrome C2 is thought to be the primary electron donor to the photosynthetic light reaction center. A number of studies have shown that the active site environment of this protein is similar to that of eurkaryotic cytochrome c. 

Staphylococcal nuclease is a rather small protein composed of a single polypeptide chain of 149 amino acids and has a molecular weight of 16,800. Both sequence (Cone et al, 1971) and three-dimensional structure (Arnone et aL, 1971) are known. Figure 5.4 shows the primary and tertiary structures. There is a single tryptophan in the sequence in position 140 (Trp 140) located very close to the C-terminus and buried in the native structure. There are also seven tyrosyl residues Tyr 91 and Tyr 93 are clearly buried in the hydrophobic core of the protein. Three helical segments are present in the native molecule. 

A number of structured databases have been developed to classify proteins according to the three-dimensional structures. Many of these are accessible via the World Wide Web, T1 protein databanlc (PDB [Bernstein d al. 1977]) is the primary source of data about the stru tures of biological macromolecules and contains a large number of structures, but many i these are of identical proteins (complexed with different ligands or determined at differet resolutions) or are of close homologues. 

Domains are formed by different combinations of secondary structure elements and motifs. The a helices and p strands of the motifs are adjacent to each other in the three-dimensional structure and connected by loop regions. Sequentially adjacent motifs, or motifs that are formed from consecutive regions of the primary structure of a polypeptide chain, are usually close together in the three-dimensional structure (Figure 2.20). Thus to a first approximation a polypeptide chain can be considered as a sequential arrangement of these simple motifs. The number of such combinations found in proteins is limited, and some combinations seem to be structurally favored. Thus similar domain structures frequently occur in different proteins with different functions and with completely different amino acid sequences. 

When one inspects the multiple channel protein sequences that have been derived, one readily recognizes that they have related primary sequences. This suggests that they have similar three-dimensional structures. The primary sequences can be subdivided into an amino-terminal, a core and a carboxy-terminal domain (see Fig. 5). Each domain seems to contribute separately to the structure and function of a given channel [49]. Following this hypothesis, it has been possible to carry out domain swapping experiments between Sh and RCK proteins [49] as well as between... 

Fig. 11.2. Schematic representation of the primary structure of secreted AChE B of N. brasiliensis in comparison with that of Torpedo californica, for which the three-dimensional structure has been resolved. The residues in the catalytic triad (Ser-His-Glu) are depicted with an asterisk, and the position of cysteine residues and the predicted intramolecular disulphide bonding pattern common to cholinesterases is indicated. An insertion of 17 amino acids relative to the Torpedo sequence, which would predict a novel loop at the molecular surface, is marked with a black box. The 14 aromatic residues lining the active-site gorge of the Torpedo enzyme are illustrated. Identical residues in the nematode enzyme are indicated in plain text, conservative substitutions are boxed, and non-conservative substitutions are circled. The amino acid sequence of AChE C is 90% identical to AChE B, and differs only in the features illustrated in that Thr-70 is substituted by Ser.

Proteins are built up by aminoacids linked by peptide bonds into a polypeptide chain (Figure 2). The sequence of the aminoacids in the chain is known as the primary structure of the protein. The primary structure of the protein gives rise to the corresponding three-dimensional structure, and the spatial relationships of the constituents are the key for the peptide function. 

---