Catalytic Triad

The term catalytic triad is used to describe the arrangement of amino acid residues in the active sites of serine proteinases that underlies their mechanism of enzyme action. It was first applied to the active site of chymotrypsin when the structure of that enzyme was determined by X-ray crystallography (1). Earlier studies had shown that chymotrypsin could be inactivated by chemical modification of one of its serine residues with the nerve gas, diisopropylfluorophosphate (DIFP). Examination of the enzyme structure revealed that the hydroxyl group of this serine, residue 195, was “activated” by the imidazole group of histidine 57, which in turn was “activated” by the carboxyl group of aspartate 102 (Fig. 1). Originally described as a charge relay system, these three residues are more commonly called a catalytic triad. 

Figure 1. The catalytic triad, the hydrolytic apparatus of serine proteinases. It consists of the side chains of an aspartic acid, a histidine, and a serine residue (eg, residues 102, 57 and 195, respectively, in bovine chymotrypsin). In the absence of substrate, the imidazole group of the histidine is unprotonated, but it potentiates the nucleophilic properties of the hydroxyl side chain of the serine. When substrate binds to the active site, the serine proton is transferred to the imidazole group and the oxygen attacks the carbonyl group of the substrate. The resulting positively charged imidazole is stabilized by interaction with the negative charge of the aspartate carboxyl group. The activated serine is also highly reactive toward inhibitors such as PMSF and DIFP.

Similar triads have been observed in both the chymotrypsin and subtilisin evolutionary families of serine proteinases (2), as well as in other hydrolytic enzymes (3). It is remarkable that the bacterial serine proteinase subtilisin has the same geometrical arrangement of aspartate, histidine, and serine residues as chymotrypsin, but all other structural aspects of the two proteins are quite different. This is a classic example of convergent evolution. The activated serine interacts with the carbonyl carbon atom of the peptide bond to be hydrolyzed, forming an oxyanion intermediate, which is converted to an acylated serine with release of the amine component of the peptide. Subsequent hydrolysis of the acylenzyme occurs by the reverse reaction in which water substitutes for the activated serine.

References

1. D. M. Blow (1976) Acc. Chem. Res. 9, 145–152. 

2. T. A. Steitz and R. G. Schulman (1982) Annu. Rev. Biochem. Biophys. 11, 419–444.

3. D. M. Blow (1990) Nature 343, 694–695.

اخر الاخبار

اخبار العتبة العباسية المقدسة

العتبة العباسية المقدسة تواصل تنظيم مجالس العزاء الصباحية بذكرى زيارة عاشوراء

مواكب العزاء تستذكر في التاسع من شهر المحرم شهادة عبدالله الرضيع بن الحسين (عليهما السلام)

العتبة العباسية المقدسة تستذكر تضحيات القاسم بن الحسن (عليهما السلام)

شعبة الحرم الشريف تواصل تنفيذ خطتها الخاصة بشهر المحرّم داخل مرقد أبي الفضل العباس (عليه السلام)

المزيد

الآخبار الصحية

لهذا السبب.. إغلاق 25 مركزًا لعلاج الإدمان في مصر ؟

خلافا للاعتقاد الشائع.. علماء يكشفون أسرار بذور البطيخ ؟!

هذا ما يحدث لجسمك عند تناولك الطماطم بانتظام !

تعرف على أطعمة تسرّع "تعافي الجسم" من حروق الشمس

المزيد

الآخبار التكنلوجية

الثلوج تغطي الصحراء الأكثر جفافا في العالم!

بتلسكوب "ألما".. التقاط صورا غير مسبوقة لبدايات الكون !

هل هاتفك مراقب؟.. 5 علامات خطيرة تكشف التجسس عليك

دبي تطلق أول رحلة تجريبية للتاكسي الجوي

المزيد

مواضيع ذات صلة

Other Attenuated Systems: Operons, Bacillus subtilis and HIV

Coupling Translation to Termination

trp Multiple Secondary Structures in trp Leader RNA

Early Explorations of the Hypersynthesis

The Serendipitous Discovery of trp Enzyme Hypersynthesis

Rapid Induction Capabilities of the trp Operon

The Aromatic Amino Acid Synthetic Pathway and its Regulation

How AraC Protein Loops and Unloops

DNA Looping and Repression of araBAD

Binding Sites of the ara Regulatory Proteins

Endoplasmic Reticulum-Associated Degradation and the Unfolded Protein Response

Protein Folding and Modifications in the Endoplasmic Reticulum