مثبط الإنزيم

HIV protease in a complex with the protease inhibitor ritonavir. The structure of the protease is shown by the red, blue and yellow ribbons. The inhibitor is shown as the smaller ball-and-stick structure near the centre. Created from PDB 1HXW.

مثبطات الأنزيم تعبير عن مركبات كيميائية ترتبط مع الأنزيم ضمن الحيوية معيقة عمله الأساسي على الركيزة والمواد الحيوية التي يعمل الأنزيم أساسا على تحويلها .

تتم عملية التثبيط إما بشكل تنافسي من قبل مركبات كيميائية تشبه الركيزة الأساسية فتنافسها على الأنزيم معطية منتجات ثانوية ، أوبشكل غير تنافسي حيث ترتبط المثبطات مع الأنزيم بروابط تكافؤية غير قابلة للكسر معطلة عمل الأنزيم بصورة نهائية ، وهذه الطريقة في التثبيط لها آثار سمية ضمن الحيوية .

المثبطات القابلة للعكس

أنواع المثبطات القابلة للعكس

Competitive inhibition: substrate (S) and inhibitor (I) compete for the active site.

Measuring the dissociation constants of a reversible inhibitor

Lineweaver–Burk plots of different types of reversible enzyme inhibitors. The arrow shows the effect of increasing concentrations of inhibitor.

أمثلة للمثبطات القابلة للعكس

Peptide-based HIV-1 protease inhibitor ritonavir

Nonpeptidic HIV-1 protease inhibitor tipranavir

المثبطات غير القابلة للعكس

أنواع التثبيط غير القابل للعكس

تفاعل المثبط غير القابل للعكس diisopropylfluorophosphate (DFP) with a serine protease

تحليل التثبيط غير القابل للعكس

مخطط حركي للمثبطات غير القابلة للعكس

حالات خاصة

Chemical mechanism for irreversible inhibition of ornithine decarboxylase by DFMO. Pyridoxal 5'-phosphate (Py) and enzyme (E) are not shown. Adapted from

أمثلة للمثبطات غير القابلة للعكس

Trypanothione reductase with the lower molecule of an inhibitor bound irreversibly and the upper one reversibly. Created from PDB 1GXF.

اكتشاف وتصميم المثبطات

Robots used for the high-throughput screening of chemical libraries to discover new enzyme inhibitors

استخدامات المثبطات

Enzyme inhibitors are found in nature and are also designed and produced as part of pharmacology and biochemistry. Natural poisons are often enzyme inhibitors that have evolved to defend a plant or animal against predators. These natural toxins include some of the most poisonous compounds known. Artificial inhibitors are often used as drugs, but can also be insecticides such as malathion, herbicides such as glyphosate, or disinfectants such as triclosan.

العلاج الكيماوي

The structure of sildenafil (Viagra)

The coenzyme folic acid (left) compared to the anti-cancer drug methotrexate (right)

The structure of a complex between penicillin G and the Streptomyces transpeptidase. Generated from PDB 1PWC.

انظر أيضاً

Transition state analog
Allosteric regulation
Enzyme assay
Medicinal chemistry
Pharmacophore
Activity-based proteomics - a branch of proteomics that uses covalent enzyme inhibitors as reporters to monitor enzyme activity.
Antimetabolite

الهامش

^ Poulin R, Lu L, Ackermann B, Bey P, Pegg AE. J Biol Chem. 1992 Jan 5;267(1):150–8. PMID 1730582

وصلات خارجية

Web tutorial on enzyme inhibition, Tutorial by Dr Peter Birch of the University of Paisley, containing very clear animations
Symbolism and Terminology in Enzyme Kinetics, Recommendations of the Nomenclature Committee of the International Union of Biochemistry (NC-IUB) on enzyme inhibition terminology
PubChem from NCBI, Database of drugs and enzyme inhibitors
BRENDA, Database of enzymes giving lists of known inhibitors for each entry
Enzymes, Kinetics and Diagnostic Use, On-line lecture concentrating on medical applications of enzyme inhibitors: by Dr. Michael W. King of the IU School of Medicine
BindingDB, a public database of measured protein-ligand binding affinities.
Enzyme Inhibition Animated Exercise (tutorial + quizzes).