Sandbox 212: Difference between revisions
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Carnitine acyltransferases carry out pivotal biological functions. All members of carnitine acyltransferases catalyze the same reversible reaction:the exchange of acyl groups between carnitine and coenzyme A (CoA). This is in accord with the fact, that the catalytic domains of all the carnitine acyltransferases are well conserved. | Carnitine acyltransferases carry out pivotal biological functions. All members of carnitine acyltransferases catalyze the same reversible reaction:the exchange of acyl groups between carnitine and coenzyme A (CoA). This is in accord with the fact, that the catalytic domains of all the carnitine acyltransferases are well conserved. | ||
However the three known classes of carnitine acyltransferases differ in their acyl group specificity | However the three known classes of carnitine acyltransferases differ in their acyl group specificity and subcellular localization(3). | ||
Carnitine acetyltransferase (CrATs) prefere '''short chain fatty acids''' as substrates and are localized in the mitochondrial matrix, the endoplasmic reticulum, and the peroxisome. | Carnitine acetyltransferase (CrATs) prefere '''short chain fatty acids''' as substrates and are localized in the mitochondrial matrix, the endoplasmic reticulum, and the peroxisome. | ||
Carnitine octanoyltransferases (COTs) show medium chain fatty acid substrate preference and are mainly found in peroxisomes. | Carnitine octanoyltransferases (COTs) show medium chain fatty acid substrate preference and are mainly found in peroxisomes. | ||
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* '''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><ref>PMID: 12526798</ref> Electrostatic interactions are formed by the carboxylate group of carnitine with the side chain guanidinium group of an arginine residue. | 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 name="structure">>PMID: 12526798</ref> 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. | ||
There are only slight conformational changes in the enzyme upon carnitine binding.“The only significant conformational difference in the active site between the free enzyme and the carnitine complex is in the side chain of <font color='#90E050'>'''serine454'''</font>, which adopts a different rotamer to have better hydrogen-bonding interactions with the carboxylate of carnitine.” <ref | There are only slight conformational changes in the enzyme upon carnitine binding.“The only significant conformational difference in the active site between the free enzyme and the carnitine complex is in the side chain of <font color='#90E050'>'''serine454'''</font>, which adopts a different rotamer to have better hydrogen-bonding interactions with the carboxylate of carnitine.” <ref name="rasmol" /></StructureSection> | ||
==Catalytic Mechanism of Carnitine Acyltransferases== | ==Catalytic Mechanism of Carnitine Acyltransferases== | ||
[[Image:Machanism fatty acid transfer.jpg|thumb|700px|left]] | [[Image:Machanism fatty acid transfer.jpg|thumb|700px|left]] | ||
