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单词 Catalytic triad
释义

Catalytic triad

中文百科

催化三联体

与底物(黑)结合的酶(TEV蛋白酶1lvm),示催化三联体的残基(红)。三联体由酸性残基(Acid)、组氨酸(His)和亲核体(Nuc)组成。在TEV蛋白酶中,酸是天冬氨酸,亲核体是半胱氨酸。
蛋白酶中常见的催化三联体电荷中继系统。酸残基(通常为谷氨酸或天冬氨酸)对齐并极化碱(通常为组氨酸),以激活亲核体(通常为丝氨酸或半胱氨酸,偶见苏氨酸)。三联体降低了亲核残基的pKa,然后进攻底物。氧阴离子穴一般会为酰胺骨架充上正电荷(偶尔为侧链),使电荷在过渡态的底物上稳定聚集
不同的氨基酸残基组合构成了各个酶中用于水解的催化三联体。左边是三联体中的亲核体、碱和酸成分。右边是不同的底物,以剪刀指示将断裂的键。β-内酰胺中可以断开两个不同的键(1:青霉素酰化酶,2:β-内酰胺酶)
半胱氨酸蛋白酶(上)与丝氨酸蛋白酶(下)催化机理之差异。其中酶分子用黑色标识,蛋白质底物用红色标识。两种机理之差异在于:(a)巯基电离 (b)酸性基团可以没有 (c)羟基脱质子与进攻协同 (d)酸、碱性基团间形成氢键 (e)离去部分与碱性基团必须精确配合 (f)丝氨酸离去基团需质子化

催化三联体通常指在水解酶和转移酶的活性位点中心同时作用的三个氨基酸残基(如蛋白酶、酰胺酶、酯酶、酰基转移酶、脂酶和β-内酰胺酶)。用于共价催化的亲核残基一般是酸-碱-亲核三联体。残基会形成一个电荷中继网络,以极化和活化亲核试剂,来进攻底物形成共价中间体,然后中间体水解,再生出游离的酶。亲核试剂大多是丝氨酸或半胱氨酸,也有少量是苏氨酸。

因为酶会折叠成复杂的三维结构,催化三联体的残基可能在其所在的氨基酸串行(一级结构)中离得很远,但最后它们将会折叠到一起。

虽然在功能上(甚至是三联体中的亲核体)进化趋异,催化三联体却是趋同进化的最好案例。对催化的化学约束使得至少23个独立的蛋白质超家族进化出了相同的催化方法。生物化学中,研究得最透彻之一的就是这些反应的作用机理。

英语百科

Catalytic triad 催化三联体

The enzyme TEV protease[lower-alpha 1] contains an example of a catalytic triad of residues (red) in its active site. The triad consists of an aspartic acid (Acid), histidine (Base) and cysteine (Nucleophile). The substrate (black) is bound by the binding site to orient it next to the triad. PDB: 1lvm​

General reaction mechanism of catalysed by a catalytic triad (black): nucleophilic substitution at a carbonyl substrate (red) by a second substrate (blue). First, the enzyme's nucleophile (X) attacks the carbonyl to form a covalently linked acyl-enzyme intermediate. This intermediate is then attacked by the second substrate's nucleophile (X'). If the second nucleophile is the hydroxyl of water, the result is hydrolysis, otherwise the result is group transfer of X'.
A catalytic triad charge-relay system as commonly found in proteases. The acid residue (commonly glutamate or aspartate) aligns and polarises the base (usually histidine) which activates the nucleophile (often serine or cysteine, occasionally threonine). The triad reduces the pKa of the nucleophilic residue which then attacks the substrate. An oxyanion hole of positively charged usually backbone amides (occasionally side-chains) stabilise charge build-up on the substrate transition state.
The range of amino acid residues used in different combinations in different enzymes to make up a catalytic triad for hydrolysis. On the left are the nucleophile, base and acid triad members. On the right are different substrates with the cleaved bond indicated by a pair of scissors. Two different bonds in beta-lactams can be cleaved (1 by penicillin acylase and 2 by beta-lactamase)

A catalytic triad refers to the three amino acid residues that function together at the centre of the active site of some hydrolase and transferase enzymes (e.g. proteases, amidases, esterases, acylases, lipases and β-lactamases). An Acid-Base-Nucleophile triad is a common motif for generating a nucleophilic residue for covalent catalysis. The residues form a charge-relay network to polarise and activate the nucleophile, which attacks the substrate, forming a covalent intermediate which is then hydrolysed to regenerate free enzyme. The nucleophile is most commonly a serine or cysteine amino acid, but occasionally threonine. Because enzymes fold into complex three-dimensional structures, the residues of a catalytic triad can be far from each other along the amino-acid sequence (primary structure), however, they are brought close together in the final fold.

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更新时间:2025/6/22 6:58:49