CHEMICAL & BIO-ORGANIC STUDIES OF VISION & PHOTOTAXIS

了解视觉传导机制，漂白适应， 和微生物的趋光性都是非常基本的问题， 生命的过程 如果可能的话， 通过各领域研究人员的努力， 整个科学领域。 我们的努力将集中在促进 这个非常困难的领域主要通过有机和生物有机的方法。 因此，它必然会集中在解释和理解 在有机结构基础上的现象。 与以往一样，我们的主要工具 将使用合成的视网膜类似物，其结构已被 这样他们就可以解决这些复杂的 现象。 我们已经做了超过90种不同的类似物，不包括 顺式/反式异构体作为单独的化合物。 具体来说，我们将调查 （a）视色素的三级结构 视紫红质 这是一种膜蛋白，尽管做了很多努力， 得到了结晶。 我们正花大力气 通过最近开发的有效的光亲和性， 标记，其将被放置在发色团的关键位点。 （B） 漂白适应机制 这种众所周知的现象远没有 比传导机制更容易理解。 我们发现了一种很好的化学物质 这将是第一次给我们一个化学处理， 研究发色团的结构因素， 漂白。 (c)维生素A异构化为11-顺式-视黄醛， 视色素发色团，是一个重要的步骤，最近进行的 发现了酶异构酶。 通过使各种类似物与 异构酶，我们计划研究异构酶机制的细节。 （d）嗜盐菌H.盐生菌依赖于两个 视网膜蛋白质，感觉视紫红质-I和11，引起有吸引力的， 鞭毛的排斥运动。 再一次， 这些光感受器的类似物为我们提供了强大的工具， 研究鞭毛运动的基本机制。 （d） 趋光单细胞藻类衣原体的光感受器已经被 被发现是最独特的，因为它是由视网膜类似物激活， 双键是固定的，因此不会发生异构化。 此外，趋光性甚至由简单分子诱导， 己醛 我们计划分离出足够数量的光感受器 蛋白质，通过基因组手段或类似物掺入和 分子生物学，使体外生物化学和生物物理 可以进行测量以阐明这些最出乎意料的结果。

Understanding the mechanisms of visual transduction, bleaching adaptation, and microbial phototaxis are all very basic questions intimately related to the process of life. An understanding, if possible, can only be achieved through the efforts of researchers in various areas covering almost the entire field of science. Our efforts will be focused in contributing to this very difficult field mainly through organic and bioorganic approaches. Thus it will necessarily be centered in interpreting and understanding the phenomena on an organic structural basis. As in the past, our major tool will be to use synthetic retinal analogs, the structures of which have been designed so that they can solve specific aspects of these complex phenomena. We have made over 90 different analogs, not counting the cis/trans isomers as separate compounds. Specifically we will investigate the following topics: (a) The tertiary structure of the visual pigment rhodopsin. This is a membrane protein, and despite many efforts it has not been obtained crystalline. We are putting a major effort in mapping out the tertiary structure by a recently developed efficient photoaffinity label, which will be placed in critical sites of the chromophore. (b)The mechanism of bleaching adaptation. This well-known phenomenon is far less understood than the transduction mechanism. We have found a good chemical handle which will for the first time give us a chemical handle to investigate the structural factors of the chromophore that lead to bleaching. (c) The isomerization of vitamin A to 11-cis-retinal, the visual pigment chromophore, is an important step performed by the recently discovered enzyme isomerase. By reacting various analogs with the isomerase, we plan to investigate the details of the isomerase mechanism. (d)The phototaxis of the halophilic bacterium H. halobium depends on two retinal proteins, sensory rhodopsin-I and 11, which cause attractive and repellent movements of the flagella. Again the incorporation of retinal analogs into these photoreceptors has provided us with powerful tools to study the basic mechanism leading to flagella movement. (d)The photoreceptor of the phototactic unicellular algae Chlamydomonas has been found to be most unique in that it is activated by retinal analogs in which the double bonds are fixed so that no isomerization can occur. Furthermore, phototaxis is even induced by simple molecules such as hexanal. We plan to isolate sufficient quantities of the photoreceptor protein, by genomic means or a combination of analog incorporation and molecular biology, so that in vitro biochemical and biophysical measurements can be performed to elucidate these most unexpected results.