Glycogenin: Difference between revisions
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<StructureSection load='3t7m' size='450' side='right' scene='' caption=''> | |||
[[Image:Glycogen_structure.png|thumb|left|350x350px|alt=Alt text|Figure 1. A cross-sectional view of glycogen with the glycogenin dimer remaining covalently attached to the non-reducing end in the centre of the globule.]] | [[Image:Glycogen_structure.png|thumb|left|350x350px|alt=Alt text|Figure 1. A cross-sectional view of glycogen with the glycogenin dimer remaining covalently attached to the non-reducing end in the centre of the globule.]] | ||
'''Glycogenin''' (Glycogenin glucosyltransferase, [[EC]] 2.4.1.186) is a [[transferase]] responsible for the biosynthesis of glycogen; an important storage form of glucose in the body. It is a unique enzyme in that it is primer, substrate, catalyst, and product of its enzymatic reaction and extension process of glycogen biosynthesis. This is initiated by its ability to transfer glucose from UDP-glucose to form an oligosaccharide of glucose units that is covalently attached to itself at Tyr-194 in a multistep reaction mechanism <ref name="one"> PMID:12051921 </ref>. It is placed in glycosyltransferase family 8 becuase it contains highly conserved motifs that are common to glycosyltransferases such as lipopolysaccharide glucose and galactose transferases and galactinol synthases <ref name="two"> PMID:9345621 </ref>. | '''Glycogenin''' (Glycogenin glucosyltransferase, [[EC]] 2.4.1.186) is a [[transferase]] responsible for the biosynthesis of glycogen; an important storage form of glucose in the body. It is a unique enzyme in that it is primer, substrate, catalyst, and product of its enzymatic reaction and extension process of glycogen biosynthesis. This is initiated by its ability to transfer glucose from UDP-glucose to form an oligosaccharide of glucose units that is covalently attached to itself at Tyr-194 in a multistep reaction mechanism <ref name="one"> PMID:12051921 </ref>. It is placed in glycosyltransferase family 8 becuase it contains highly conserved motifs that are common to glycosyltransferases such as lipopolysaccharide glucose and galactose transferases and galactinol synthases <ref name="two"> PMID:9345621 </ref>. | ||
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==Protein Function== | ==Protein Function== | ||
<scene name='44/445344/Cv/1'>Figure 2. Glycogenin Monomer with UDP-glucose and Manganese</scene> (PDB entry [[1ll2]]). | |||
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'''UDP-alpha-D-glucose + glycogenin <-> UDP + alpha-D-glucosylglycogenin''' | '''UDP-alpha-D-glucose + glycogenin <-> UDP + alpha-D-glucosylglycogenin''' | ||
The glycogenin binds <scene name='Sandbox_Reserved_343/Udp-glucose_and_manganese/2'>UDP-glucose and manganese</scene> at the Tyr-194 in <scene name='Sandbox_Reserved_343/Udp-glucose_and_manganese/3'>between the alpha/beta sandwich</scene> and then the enzyme is primed for extension by subsequent UDP-glucose additions for glycogen formation. The glucosyltransferase activity of glycogenin catalyzes the addition of subsequent UDP-glucose monomers to form a glucose polymer roughly 7 residues long. The reaction is then joined by the enzyme glycogen synthase which continues the α-1,4-glycosidic elongation of the glucose polymers, and glycogen branching enzyme that catalyzes α-1,6-glycosidic branch formation of the glycogen. The Mn2+ cation functions as a lewis acid to stabilize the UDP leaving group and help fascilitate the transfer from the Tyr-194 to another nucleophilic intermediate acceptor, Asp-162, in a dual-step nucleophilic SN1 substitution reaction <ref name="one" />. | The glycogenin binds <scene name='Sandbox_Reserved_343/Udp-glucose_and_manganese/2'>UDP-glucose and manganese</scene> at the Tyr-194 in <scene name='Sandbox_Reserved_343/Udp-glucose_and_manganese/3'>between the alpha/beta sandwich</scene> and then the enzyme is primed for extension by subsequent UDP-glucose additions for glycogen formation. The glucosyltransferase activity of glycogenin catalyzes the addition of subsequent UDP-glucose monomers to form a glucose polymer roughly 7 residues long. The reaction is then joined by the enzyme glycogen synthase which continues the α-1,4-glycosidic elongation of the glucose polymers, and glycogen branching enzyme that catalyzes α-1,6-glycosidic branch formation of the glycogen. The Mn2+ cation functions as a lewis acid to stabilize the UDP leaving group and help fascilitate the transfer from the Tyr-194 to another nucleophilic intermediate acceptor, Asp-162, in a dual-step nucleophilic SN1 substitution reaction <ref name="one" />. | ||
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Glycogenin has been identified in two human isoforms. Glycogenin-1 is a 37kDa muscle isoform encoded for by the gene GYG1, whereas glycogenin-2 is the 66kDa liver isoform that is encoded by the gene GYG2 and expressed primarily in cardiac muscle <ref name="five"> PMID:20357282 </ref>. Mutations of the GYG1 gene results in a loss of the autoglycosylation capabilities of glycogenin for initiating glycogen synthesis in muscle, which leads to problems such as cardiac arrhythmia and muscle weakness due to depleted or abnormal storage of glycogen in heart and skeletal muscle <ref name="five" />. | Glycogenin has been identified in two human isoforms. Glycogenin-1 is a 37kDa muscle isoform encoded for by the gene GYG1, whereas glycogenin-2 is the 66kDa liver isoform that is encoded by the gene GYG2 and expressed primarily in cardiac muscle <ref name="five"> PMID:20357282 </ref>. Mutations of the GYG1 gene results in a loss of the autoglycosylation capabilities of glycogenin for initiating glycogen synthesis in muscle, which leads to problems such as cardiac arrhythmia and muscle weakness due to depleted or abnormal storage of glycogen in heart and skeletal muscle <ref name="five" />. | ||
</StructureSection> | |||
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==3D structures of glycogenin== | ==3D structures of glycogenin== | ||
