Sequence structural deductions from

Green, N.M. (1990). Structural deductions from receptor sequences. In Receptor Biochemistry a Practical Approach. 

Since that time many more sequences have become available through the advent of recombinant DNA technology and the deduction of amino acid sequences from the base sequences of cloned DNA. At the present time, the primary structures (amino acid sequences) of 14 proteins of the transferrin family have been established. These include seven serum transferrins, from human 10, 36), pig (37), horse 38), rabbit 39), toad Xenopus laevis) 40), sphinx moth (M. sexta) 13), and cockroach Blaberus discoidalis 4) chicken 34, 35) and duck 41) ovotransfer-rins four lactoferrins, from human (11, 42), mouse 43), pig 44) and cattle 45, 46) and the human tumor cell melanotransferrin 47). All of these sequences are available from sequence databases such as EMBL and SWISSPROT. 

The most intensively investigated dehydroxylation is probably the reaction of Mg(OH)2, though detailed results are also available for the hydroxides of certain other divalent cations. Several summaries of the mechanistic deductions obtained from such work, including literature sources, were presented at a conference at Dijon in 1974 [87]. The extensive literature concerned with the thermal analysis of hydroxides has been reviewed by Dollimore [79] who has also included the behaviour of oxides. Water elimination can be regarded as the first in a sequence of structurally related steps through which the hydroxide is converted into the thermally most stable oxide. 

The method employed for an initial effort to explore a complex reaction sequence should be fast and inexpensive, but sufficiently reliable to enable meaningful deductions concerning structures and relative energies to be made. The results can then be usefully employed as starting points for more elaborate and accurate methods for detailing the energy hypersurfaces. For this study we have chosen to use Anderson s modification (27) of extended Hiickel theory (MEHT). MEHT differs from EHT by the inclusion of a pair-wise correction for atom-atom repulsions. 

So far, we started from a logical structure and asked which final states (stable or periodic) are consistent with this structure, by which sequences of states they can be reached and which conditions determine the pathway that will be followed. In opposition with this analytic, deductive approach, one can start from an observed (or desired) behavior and try to proceed... 

These models start from the most comprehensive structural information available. Since there is no X-ray diffraction structure yet, this comes principally from polypeptide linear sequence data and deductions therefrom. Two major structural proposals (see Chapter 11) are from Zuber and colleagues (B800-850, B875, B1015) [31] and from Loach and co-workers (B875) [33]. A proposal based on a mix of structural and spectroscopic information comes from Kraimer et al. [34]. 

Figure 10.1. The central dogma. Proceeding from the DNA through the RNA to the protein level, various sequence features and modifications can be identified that can be used in the computational deduction of gene structure. These include the presence of promoter and regulatory regions, intron-exon boundaries, and both start and stop signals. Unfortunately, these signals are not always present, and, when they are present, they may not always be in the same form or context. The reader is referred to the text for greater detail.

The alignment in Table I includes sequences from 12 different zymogens and enzymes, only two of which are known completely and a third is almost completed. Despite the fragmentary data, we are able to deduct some general structure-function relationships of the aspartate proteinases and of the gastric zymogens. 

Chart VIII-8. The complete amino-acid sequences deduced for clupeine Y l, Yll and Z with illustration of several degradations. (Structures of tryptic peptides obtained from whole clupeine from Clupea harengus were also referred to for this deduction. See text) (A = Arg) (Chang, 1969 Chang, Nakahara, and Ando, to be published)... 

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