Model Study on Asymmetry-Inducing and Recognizing Ability of Peptide Chains

肽链不对称诱导与识别能力的模型研究

• 批准号: 09450344
• 负责人: OHKATSU Yasukatsu
• 金额: $ 9.02万
• 依托单位: Kogakuin University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09450344/
• 关键词: Cytochrome p-450; Hydrolase model; esterase model; α-helix; conformation; porphyrin; asymmetric recognition; 不斉識別; 糖蛋白質; エステル化; βシート; 不斉誘導; ペプチド鎖; 糖蛋白質モデル; 加水分解; α-ヘリックス; D,L-アミノ酸エステル; チトクロームP-450; 面区別; エポキシ化

The function of an enzyme consisting of proteins is explained by 'lock and key' theory, which is convenient to explain specificities of the enzyme, but it cannot explain fast enzymatic reaction. The applicant assumed that the conformation of peptide chains around the active site of an enzyme provides the specificity of enzyme, even if the space around active site is wide or is not controlled by peptide chains, and has gotten a few evidences that this assumption is correct on basis of model reactions. In first year, porphyrin complexes having peptide chains on the meso positions were synthesized as model of cytochrome P-450. These are completely different from models proposed so far, at the point that it has a wide space around active site, but nevertheless attained high asymmetric induction and high reaction rates at the same time, especially depending on the content of α-helix.. In second year, the applicant found that several glycoproteins are models of α-chymotrypsin and also found that they recognize R,S-configuration of amino acids by a-helix of the peptide conformation. In this year, a kind of glycoproteins were found to be esterase models in non-aqueous medium, but they do not seem to induce asymmetry of esterification products on basis of the β-sheet conformation.As mentioned above, it is proposed that the specificity of an enzyme is derived from α-helix of peptide chains, even if the space around the active site is not narrow as taught by 'key and lock' theory.

由蛋白质组成的酶的功能用“锁和钥匙”理论来解释，这便于解释酶的特异性，但不能解释快速的酶促反应。申请人假设酶活性位点周围的肽链构象提供了酶的特异性，即使活性位点周围的空间很宽或不受肽链控制，并且已经基于模型反应得到了一些证据证明该假设是正确的。在第一年，卟啉配合物的meso位置上的肽链合成作为模型的细胞色素P-450。这与迄今为止提出的模型完全不同，在这一点上，它在活性位点周围具有宽的空间，但仍然同时获得高的不对称诱导和高的反应速率，特别是取决于α-螺旋的含量。第二年，申请人发现几种糖蛋白是α-糜蛋白酶的模型，并且还发现它们通过肽构象的α-螺旋识别氨基酸的R，S-构型。近年来，人们发现了一类糖蛋白在非水介质中作为酯酶模型，但它们并不能诱导基于β-折叠构象的酯化产物的不对称性，由此提出，即使活性位点周围的空间并不像“钥匙和锁”理论所教导的那样狭窄，酶的特异性也来自于肽链的α-螺旋。

项目成果

Y.Ohkatsu and D.Higo: "Hydrolyses of Amino Acid Esters by Glycoprotein Models" Yukagakkaishi. in contribution.

Y.Ohkatsu 和 D.Higo：“糖蛋白模型对氨基酸酯的水解”Yukagakkaishi。

Y. Ohkatsu, T. Watanabe, M. Hayakawa: "Comparison of Two Types of Cytochrome P-450 Models. Effect of Steric Hindrance near Active Sites"Yukagaku. 47. 557-584 (1998)

Y. Ohkatsu、T. Watanabe、M. Hayakawa：“两种细胞色素 P-450 模型的比较。活性位点附近空间位阻的影响”Yukagaku。