Sandbox 212: Difference between revisions
Ndeye Coumba (talk | contribs) No edit summary |
Ndeye Coumba (talk | contribs) No edit summary |
||
| Line 6: | Line 6: | ||
Carnitine acyltransferases are a large family of enzymes that play a main role in cellular energy metabolism, i.e. fatty acid oxidation. These enzymes catalyze the reversible exchange of acyl groups between coenzyme A and carnitine. | Carnitine acyltransferases are a large family of enzymes that play a main role in cellular energy metabolism, i.e. fatty acid oxidation. These enzymes catalyze the reversible exchange of acyl groups between coenzyme A and carnitine. | ||
Carnitine acyltransferases include three different classes of enzymes which are known as carnitine acetyltransferases (CrATs), carnitine octanoyltransferases (CrOTs) and carnitine palmityltransferase (CPTs). The three classes differ in their acyl group specificity as well as their localization. | Carnitine acyltransferases include three different classes of enzymes which are known as carnitine acetyltransferases (CrATs), carnitine octanoyltransferases (CrOTs) and carnitine palmityltransferase (CPTs). The three classes differ in their acyl group specificity as well as their localization. | ||
Mavis Agbandje-McKenna§, and Robert McKenna§¶.Structure of Human Carnitine Acetyltransferase.Published, JBC Papers in Press, January 31, 2003. [http://dx.doi.org/DOI10.1074/jbc.M21235620DOI:DOI10.1074/jbc.M21235620] | Donghai Wu‡, Lakshmanan Govindasamy§, Wei Lian‡, Yunrong Gu‡, Thomas Kukar‡, | ||
Mavis Agbandje-McKenna§, and Robert McKenna§¶.Structure of Human Carnitine Acetyltransferase.Published, JBC Papers in Press, January 31, 2003. [http://dx.doi.org/DOI10.1074/jbc.M21235620DOI:DOI10.1074/jbc.M21235620] | |||
In this entry we will focus on the structure of carnitine acetyltransferase as a representitive of carnitine acyltransferases. Determining the structure and thus the molecular basis for fatty acid transfer is needed for drug development.Being major enzymes in fatty acid oxidation carnitine acyltransferases are viewed as promising targets which can be used to develop successful therapeutics against type 2 diabetes, obesity and other human diseases. | In this entry we will focus on the structure of carnitine acetyltransferase as a representitive of carnitine acyltransferases. Determining the structure and thus the molecular basis for fatty acid transfer is needed for drug development.Being major enzymes in fatty acid oxidation carnitine acyltransferases are viewed as promising targets which can be used to develop successful therapeutics against type 2 diabetes, obesity and other human diseases. | ||
| Line 38: | Line 40: | ||
* '''carnitine binding site''' | * '''carnitine binding site''' | ||
The carnitine substrate has to be positioned in a way that the proton of its hydroxyl group can interact with the nitrogen N3 of the catalytic residue histidine 343. Carnitine binding in the right position is made possible by electrostatic interactions and the formation of hydrogen bondings between the '''carboxylate group''' of carnitine and residues near the active site. The residues that form the carnitine binding site can be found in the C domain and in the N domain. | The carnitine substrate has to be positioned in a way that the proton of its hydroxyl group can interact with the nitrogen N3 of the catalytic residue histidine 343. Carnitine binding in the right position is made possible by electrostatic interactions and the formation of hydrogen bondings between the '''carboxylate group''' of carnitine and residues near the active site. The residues that form the carnitine binding site can be found in the C domain and in the N domain. | ||
The main <scene name='Sandbox_212/Hydrogen_bonding_residues/3'>residues involved in hydrogen-bonding interactions </scene> are <font color='#0000FF'>'''tyrosine452'''</font>, <font color='#90E050'>'''serine454'''</font>, and <font color='#FF0D0D'>'''threonine465'''</font>. They possess side chain hydroxyls which can interact with the carboxylic oxygen atoms of carnitine. One of the carboxylic oxygen atoms is also hydrogen-bonded to a <font color='#00007C'>'''water molecule '''</font> | The main <scene name='Sandbox_212/Hydrogen_bonding_residues/3'>residues involved in hydrogen-bonding interactions </scene> are <font color='#0000FF'>'''tyrosine452'''</font>, <font color='#90E050'>'''serine454'''</font>, and <font color='#FF0D0D'>'''threonine465'''</font>. They possess side chain hydroxyls which can interact with the carboxylic oxygen atoms of carnitine. One of the carboxylic oxygen atoms is also hydrogen-bonded to a <font color='#00007C'>'''water molecule '''</font><ref>PMID: 12526798</ref> Electrostatic interactions are formed by the carboxylate group of carnitine with the side chain guanidinium group of an arginine residue. | ||
Electrostatic interactions are formed by the carboxylate group of carnitine with the side chain guanidinium group of an arginine residue. | |||
The exact role of the '''trimethylammonium group''' during carnitine binding hasn’t been fully revealed yet. Carnitine is rather required for catalysis than for binding. Even though the trimethylammonium group has a positive charge on its nitrogen it is not surrounded by negatively charged residues which could balance it. Instead, the trimethylammonium group is situated in a rather hydrophobic environment. | The exact role of the '''trimethylammonium group''' during carnitine binding hasn’t been fully revealed yet. Carnitine is rather required for catalysis than for binding. Even though the trimethylammonium group has a positive charge on its nitrogen it is not surrounded by negatively charged residues which could balance it. Instead, the trimethylammonium group is situated in a rather hydrophobic environment. | ||