Kinase

From The School of Biomedical Sciences Wiki
(Difference between revisions)
Jump to: navigation, search
 
Line 1: Line 1:
=== What is a Kinase?  ===
 
 
 
A kinase is an [[Enzyme|enzyme]] that catalyses the addition of [[Phosphate|phosphate groups]] ([[Phosphorylation|phosphorylation]]) to specific substrates using ATP, forming a [[Covalent bond|covalent bond]] with this [[Substrate|substrate]]<ref>Molecular biology of the cell (5th edition), Alberts et al. Garland Science, 2008</ref>. There are currently 518 known protein kinase genes in the [[Human genome|human genome]]<ref name="null">Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S (2002) The protein kinase complement of the human genome. Science 298: 1912-1934</ref>. Furthermore, kinases are commonly found in [[Cell signalling pathways|cell signalling pathways]], where they will activate or deactivate [[Enzymes|enzymes]]. An example of cell signalling of this sort is when the [[Hormone|hormone]] [[Epinephrine|epinephrine]] is released and a series of kinases will activate the [[Phosphorylase A|phosphorylase A]] and deactivate [[Glycogen synthase|glycogen synthase]] A to aid in the [[Hydrolysis|hydrolysis]] of [[Glycogen|glycogen]] into [[Glucose|glucose]] to provide energy<ref>Berg JM, Tymoczko JL, Stryer L. Biochemistry. 5th edition. New York: W H Freeman; 2002. Section 21.3, Epinephrine and Glucagon Signal the Need for Glycogen Breakdown. Available from: https://www.ncbi.nlm.nih.gov/books/NBK22429/</ref>.  
 
A kinase is an [[Enzyme|enzyme]] that catalyses the addition of [[Phosphate|phosphate groups]] ([[Phosphorylation|phosphorylation]]) to specific substrates using ATP, forming a [[Covalent bond|covalent bond]] with this [[Substrate|substrate]]<ref>Molecular biology of the cell (5th edition), Alberts et al. Garland Science, 2008</ref>. There are currently 518 known protein kinase genes in the [[Human genome|human genome]]<ref name="null">Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S (2002) The protein kinase complement of the human genome. Science 298: 1912-1934</ref>. Furthermore, kinases are commonly found in [[Cell signalling pathways|cell signalling pathways]], where they will activate or deactivate [[Enzymes|enzymes]]. An example of cell signalling of this sort is when the [[Hormone|hormone]] [[Epinephrine|epinephrine]] is released and a series of kinases will activate the [[Phosphorylase A|phosphorylase A]] and deactivate [[Glycogen synthase|glycogen synthase]] A to aid in the [[Hydrolysis|hydrolysis]] of [[Glycogen|glycogen]] into [[Glucose|glucose]] to provide energy<ref>Berg JM, Tymoczko JL, Stryer L. Biochemistry. 5th edition. New York: W H Freeman; 2002. Section 21.3, Epinephrine and Glucagon Signal the Need for Glycogen Breakdown. Available from: https://www.ncbi.nlm.nih.gov/books/NBK22429/</ref>.  
  
Line 7: Line 5:
 
It is very difficult to perform enzyme reaction analysis due to the limited methods available alongside the fact that large protein catalysts are highly complex. Over the recent decades, many studies have been carried out in terms of the action of kinases, such as energy studies that measured the Bronsted nucleophile coefficient to aid in understanding the transition state. By substituting flurorine atoms on the phenol ring it was possible to study tyrosine kinase activity, this proved that phosphoryl transfer rate is almost indepent of the nucleophiole pKa<ref>Kim K, Cole PA. Measurement of a Brønsted nucleophile coefficient and insights into the transition state for a protein tyrosine kinase. Journal of the American Chemical Society. 1997;119:11096–11097</ref>. It is possible to identify active states of kinases by crystallography using macroscopic and microscopic features required for phosphoryl transfer. This is due to the fact that a hydrophobic spine is created when N terminal and C terminal lobes interact which in turn interact with kinases<ref>Surface comparison of active and inactive protein kinases identifies a conserved activation mechanism. Kornev AP, Haste NM, Taylor SS, Eyck LF Proc Natl Acad Sci U S A. 2006 Nov 21; 103(47):17783-8.</ref>.  
 
It is very difficult to perform enzyme reaction analysis due to the limited methods available alongside the fact that large protein catalysts are highly complex. Over the recent decades, many studies have been carried out in terms of the action of kinases, such as energy studies that measured the Bronsted nucleophile coefficient to aid in understanding the transition state. By substituting flurorine atoms on the phenol ring it was possible to study tyrosine kinase activity, this proved that phosphoryl transfer rate is almost indepent of the nucleophiole pKa<ref>Kim K, Cole PA. Measurement of a Brønsted nucleophile coefficient and insights into the transition state for a protein tyrosine kinase. Journal of the American Chemical Society. 1997;119:11096–11097</ref>. It is possible to identify active states of kinases by crystallography using macroscopic and microscopic features required for phosphoryl transfer. This is due to the fact that a hydrophobic spine is created when N terminal and C terminal lobes interact which in turn interact with kinases<ref>Surface comparison of active and inactive protein kinases identifies a conserved activation mechanism. Kornev AP, Haste NM, Taylor SS, Eyck LF Proc Natl Acad Sci U S A. 2006 Nov 21; 103(47):17783-8.</ref>.  
  
'''Some Common Kinases:'''
+
=== Some Common Kinases ===
 
+
[[Protein kinase A|Protein Kinase A]] - involved in cAMP-Dependant phosphorylation cascade
+
 
+
[[Protein Kinase C|Protein Kinase C]] - involved in Signal cascades which release DAG, IP3 and Calcium ions
+
 
+
[[Glycogenolysis|Glycogen Phosphorylase Kinase]] - involved in regulation of blood glucose concentration by activating Glycogen phosphorylase which depolymerises Glycogen
+
 
+
[[Cell_cycle|Cyclin Dependant Kinases]] - involved in regulation of cell cycle and the progession between each phase
+
 
+
<br>
+
  
<br>  
+
*[[Protein kinase A|Protein Kinase A]] - involved in cAMP-Dependant phosphorylation cascade
 +
*[[Protein Kinase C|Protein Kinase C]] - involved in Signal cascades which release DAG, IP3 and Calcium ions
 +
*[[Glycogenolysis|Glycogen Phosphorylase Kinase]] - involved in regulation of blood glucose concentration by activating Glycogen phosphorylase which depolymerises Glycogen
 +
*[[Cell cycle|Cyclin Dependant Kinases]] - involved in regulation of cell cycle and the progession between each phase<br>
  
 
=== References  ===
 
=== References  ===
  
 
<references />
 
<references />

Latest revision as of 20:12, 10 December 2018

A kinase is an enzyme that catalyses the addition of phosphate groups (phosphorylation) to specific substrates using ATP, forming a covalent bond with this substrate[1]. There are currently 518 known protein kinase genes in the human genome[2]. Furthermore, kinases are commonly found in cell signalling pathways, where they will activate or deactivate enzymes. An example of cell signalling of this sort is when the hormone epinephrine is released and a series of kinases will activate the phosphorylase A and deactivate glycogen synthase A to aid in the hydrolysis of glycogen into glucose to provide energy[3].

Studying Kinase Activity

It is very difficult to perform enzyme reaction analysis due to the limited methods available alongside the fact that large protein catalysts are highly complex. Over the recent decades, many studies have been carried out in terms of the action of kinases, such as energy studies that measured the Bronsted nucleophile coefficient to aid in understanding the transition state. By substituting flurorine atoms on the phenol ring it was possible to study tyrosine kinase activity, this proved that phosphoryl transfer rate is almost indepent of the nucleophiole pKa[4]. It is possible to identify active states of kinases by crystallography using macroscopic and microscopic features required for phosphoryl transfer. This is due to the fact that a hydrophobic spine is created when N terminal and C terminal lobes interact which in turn interact with kinases[5].

Some Common Kinases

References

  1. Molecular biology of the cell (5th edition), Alberts et al. Garland Science, 2008
  2. Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S (2002) The protein kinase complement of the human genome. Science 298: 1912-1934
  3. Berg JM, Tymoczko JL, Stryer L. Biochemistry. 5th edition. New York: W H Freeman; 2002. Section 21.3, Epinephrine and Glucagon Signal the Need for Glycogen Breakdown. Available from: https://www.ncbi.nlm.nih.gov/books/NBK22429/
  4. Kim K, Cole PA. Measurement of a Brønsted nucleophile coefficient and insights into the transition state for a protein tyrosine kinase. Journal of the American Chemical Society. 1997;119:11096–11097
  5. Surface comparison of active and inactive protein kinases identifies a conserved activation mechanism. Kornev AP, Haste NM, Taylor SS, Eyck LF Proc Natl Acad Sci U S A. 2006 Nov 21; 103(47):17783-8.
Personal tools
Namespaces
Variants
Actions
Navigation
Toolbox