Portal de Periódicos da CAPES

The Application of Chemical Studies of Human Chorionic Gonadotropin to Visualize Its Three-Dimensional Structure*

1993; Oxford University Press; Volume: 14; Issue: 3 Linguagem: Inglês

10.1210/edrv-14-3-291

1945-7189

Joyce W. Lustbader, David L. Yarmush, Steven Birken, David Puett, Robert E. Canfield,

Hypothalamic control of reproductive hormones

ALTHOUGH the primary structures (amino acid sequences) of each human and many mammalian gonadotropins were determined decades ago, their three-dimensional structures remain unknown. Since the demonstration by Anfinsen (1) that the information for generating the structure of a protein exists within the amino acid sequence alone, protein chemists have tried to decipher that information but have not yet succeeded. Although some successful methods have been devised to predict secondary structural elements from knowledge of the primary structure, little success has been achieved in generating a complete threedimensional model solely from the amino acid sequence. It is pertinent to inquire whether there is an intermediate solution to this important problem. Suppose, for example, that one has a large body of chemical and immunochemical information which permits the selection and modification of structural motifs that are based on models of likely loop structures in the protein and are consistent with the body of known information. Can such a very rough model be refined by computer algorithms into potentially real structures which can then be tested by experiments? Essentially, the question is whether one can use the computer to process biological and chemical information to generate a testable model of a protein structure. Such a model would be of great use to endocrinologists studying the glycoprotein hormones and would help in the design of structure-function studies, immunochemical measuring systems, and recombinant constructs. Essentially, such a three-dimensional image may prompt investigators to develop new hypotheses and experiments that may not have been apparent without such a visual aid. This is the purpose of presenting such a model in this review.