FORMATION AND STABILIZATION OF PROTEIN STRUCTURE
FORMATION AND STABILIZATION OF PROTEIN STRUCTURE
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DOI：
10.1042/bj1280737
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发表时间：
1972-01-01
影响因子：
4.1
通讯作者：
ANFINSEN, CB
中科院分区：
文献类型：
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作者：
ANFINSEN, CB
蛋白质分子的研究通常分为三大类之一：从游离氨基酸组装多肽链，将链折叠成独特的三维物体以及溶液中的详细几何形状与生物功能之间的关系。最后两个，加上酶催化的分子机制的信息，构成了蛋白质化学存在的理由。酶学家和蛋白质化学家的最终目标是能够合成一个氨基酸序列，当允许折叠时，它将呈现一个稳定的预先设计的三维原子排列，能够进行所需的催化作用。生物化学学会邀请我讨论我和我的同事们在过去几年中所做的可能有助于最终实现这一目标的一些工作，我感到非常荣幸。上述第一类问题，涉及到将氨基酸组装成由细胞遗传物质指定的序列，现在几乎已经解决了。这是保罗·扎梅尼克（Paul Zamecnik，1962）和戈宾德·霍拉纳（Ghobind Khorana，1968）在本系列早期讲座中直接或间接的主题，并且仍然是生物化学家和分子生物学家的主要兴趣，他们继续填补核酸相互作用和代谢控制的细节。我们现在对核糖体-mRNA复合物如何从N端到C端排列多肽链有了很大的了解，在高等生物体中大约是1个残基/秒，在微生物中大约快一两个数量级，蛋白质研究的另外两个方面，即折叠和功能，是非常密切相关的。随着我们的复杂性的增加，很明显，蛋白质结构中没有多少表面的渣滓。通过基于功能的自然选择，进化已经消除了大部分不需要的东西（尽管很难对此进行分类;体外实验表明，某些结构部分可以在不丧失功能的情况下被消除，但这些结构可能在体内实现微妙和基本的功能）。虽然
Studies of protein molecules generally fall into one of three broad categories: polypeptide chain assembly from free amino acids, the folding of the chain into a unique three-dimensional object and the relationships between detailed geometry in solution and biological function. The last two, together with information on the molecular mechanism of enzymic catalysis, constitute the raison d'etre of protein chemistry. The ultimate aim of the enzymologist and the protein chemist is to be able to synthesize an amino acid sequence that, when allowed to fold, will assume a stablepredesigned three-dimensional arrangement of atoms capable of carrying out the desired catalytic act. It is a great honour to have been asked by the Biochemical Society to discuss some of the work that my colleagues and I have done over the past years that might contribute to the ultimate achievement of this goal. The first category above, involving the assembly of amino acids into the sequence specified by the genetic material of the cell, is by now almost solved. It was the direct or indirectsubject matter of the earlier Lectures in this series given byPaul Zamecnik (1962) and by Ghobind Khorana (1968), and remains of major interest to biochemists and molecular biologists who continue to fill in thedetails of nucleic acid interactions and metabolic control. We now know a great deal about how ribosome-mRNA complexes lay down the polypeptide chain from the N-terminus to the C-terminus, ata rate of about 1 residue/s per site in higher organisms and about one or two orders ofmagnitude more rapidly in micro-organisms.The other two aspects of the study of proteins, namely folding and function, are very closely related. As our sophistication has increased it has become apparent that not much superficial dross remains in the fabric of proteins. Evolution, through natural selection basedon function, has eliminated most of what is not needed (although it is difficult to be categorical about this; experiments carried out in vitro suggest that certain portions of structure may be eliminated without loss of function, but these may fulfil subtle and essential functions in vivo). Although