Isocitrate dehydrogenase: Difference between revisions

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== '''Isocitrate Dehydrogenase''' ==
[[Image:1sjs.png|left|200px|thumb|Crystal Structure of Isocitrate dehydrogenase, [[1sjs]]]]
== ''' Overview:'''==
{{STRUCTURE_1sjs|  PDB=1sjs  | SIZE=300| SCENE= |right|CAPTION=Isocitrate dehydrogenase, [[1sjs]] }}


Isocitrate Dehydrogenase is an enzyme that is used during the third step of the [http://en.wikipedia.org/wiki/Citric_acid_cycle citric acid cycle]. This biological reaction is an essential process that is used to create molecules that are used for cellular energy. In this step it catalyzes the oxidative decarboxylation of isocitrate meaning that CO2 is released from the isocitrate. In addition coenzyme [http://en.wikipedia.org/wiki/Nicotinamide_adenine_dinucleotide NAD]+ is converted to an [http://en.wikipedia.org/wiki/Nicotinamide_adenine_dinucleotide NADH]. This reaction results in an alpha-ketoglutarate molecule which is then moved on to the forth step of the citric acid cycle.  
 
[[Isocitrate dehydrogenase]] (IDH) is an enzyme that is used during the third step of the [http://en.wikipedia.org/wiki/Citric_acid_cycle citric acid cycle]. This biological reaction is an essential process that is used to create molecules that are used for cellular energy. In this step it catalyzes the oxidative decarboxylation of isocitrate meaning that CO2 is released from the isocitrate. In addition coenzyme [http://en.wikipedia.org/wiki/Nicotinamide_adenine_dinucleotide NAD]+ is converted to an [http://en.wikipedia.org/wiki/Nicotinamide_adenine_dinucleotide NADH]. This reaction results in an alpha-ketoglutarate molecule which is then moved on to the forth step of the citric acid cycle. In ''Escherichia coli'' the IDH is regulated by phosphorylation which is catalyzed by [[Isocitrate dehydrogenase kinase/phosphatase|IDH kinase/phosphatase (IDHK/P)]]. The images at the left and at the right correspond to one representative Isocitrate dehydrogenase, ''i.e.'' the crystal structure of Isocitrate dehydrogenase from ''Escherichia coli'' ([[1sjs]]). 
 
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== '''Structure:'''==
== '''Structure:'''==


Isocitrate dehydrogenase is SCOP classified as an alpha beta structure. Its secondary composition consists of mainly alpha helices and beta sheets which are arranged into three layer alpha beta alpha <scene name='Michael_nobbe_sandbox_2/Alpha_beta_sandwich/1'>sandwich structures.</scene>. The entire protein consists of two side by side sandwich structures that face opposite directions. This then causes the proteins two active sites to face opposite directions. These two groups make up the A and B subunits of isocitrate dehydrogenase.In human isocitrate dehydrogenase there are 4 subunits.
Isocitrate dehydrogenase is SCOP classified as an alpha beta structure. Its secondary composition consists of mainly alpha helices and beta sheets which are arranged into three layer alpha beta alpha <scene name='Michael_nobbe_sandbox_2/Alpha_beta_sandwich/1'>sandwich structures.</scene>. The entire protein consists of two side by side sandwich structures that face opposite directions. This then causes the proteins two active sites to face opposite directions. These two groups make up the A and B subunits of isocitrate dehydrogenase.In human isocitrate dehydrogenase there are 4 subunits.


                                                                                         {{STRUCTURE_1t0l |  PDB=1t0l  |  SCENE=  }}
                                                                                          
{{STRUCTURE_1t0l |  PDB=1t0l  |  SCENE=  }}


=='''The Active Site'''==
=='''The Active Site'''==
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=='''Inhibition'''==
=='''Inhibition'''==
This step an irreversible reaction. It must be carefully regulated to avoid depletion of isocitrate in the body. The reaction is started by substrate availability which are: isocitrate,Mg2+, NAD+ or NADP+. If these are not present than the process will not carry forward. The reaction is inhibited by the removal of NADH from the presence of the citric acid cycle. The product is also inhibited by ATP feedback. This feedback inhibition is a competitive inhibitor. Since the citric acid cycle is used to produce energy molecules (ATP), an abundance of product will shut down the cycle.
This step an irreversible reaction. It must be carefully regulated to avoid depletion of isocitrate in the body. The reaction is started by substrate availability which are: isocitrate,Mg2+, NAD+ or NADP+. If these are not present than the process will not carry forward. The reaction is inhibited by the removal of NADH from the presence of the citric acid cycle. The product is also inhibited by ATP feedback. This feedback inhibition is a competitive inhibitor. Since the citric acid cycle is used to produce energy molecules (ATP), an abundance of product will shut down the cycle.
== 3D Structures of Isocitrate dehydrogenase  ==
=== IDH ===
1pb3, 1sjs, 6icd , 7icd, 3icd– EcIDH - Escherichia coli
3blx – yIDH – yeast
1zor – IDH – Thermotoga maritima
2b0t – IDH – Corynebacterium glutamicum
1xgv , 1v94– ApIDH - Aeropyrum pernix
3dms – IDH – Burkholderia pseudomallei
2uxq – DpIDH – Desulfotalea psychrophila
1idd, 1idf - EcIDH (mutant)
2iv0 – IDH+Zn++ - Archaeoglobus fulgidus
=== IDH+NADP ===
1pb1, 9icd, 4icd – EcIDH+NADP
1iso – EcIDH (mutant)+NAD
3inm – hIDH+NADPH – human
1t09 – hIDH+NADP
2qfv – yIDH+NADP
2e5m, 2e0c – IDH+NADP – Sulfolobus tokodaii
2cmj – mIDH+NADP – mouse
1tyo – ApIDH+NADP
1j1w – AvIDH+NADP – Azotobacter vinelandii
=== IDH+NADP+ion ===
1bl5 – EcIDH+NADP+Mg++
1hj6 – EcIDH (mutant)+NADP+Mg++
=== IDH+isocitrate ===
1cw1 - EcIDH (mutant)+isocitrate+Mn++
1gro, 1grp - EcIDH (mutant)+isocitrate+Mg++
1cw7 – EcIDH+isocitrate+Mn++
5icd, 8icd – EcIDH+isocitrate+Mg++
1cw7 – EcIDH+isocitrate+Mn++
5icd, 8icd – EcIDH+isocitrate+Mg++
1p8f – EcIDH+isocitrate
1t0l - hIDH+NADP+isocitrate+Ca++ 
2qfw – yIDH+isocitrate
3blv – yIDH+citrate
3blw – yIDH+citrate+AMP
2uxr – DpIDH+isocitrate
1itw – AvIDH+isocitrate+Mn++
1lwd – IDH+isocitrate+Mn++ - pig
1hqs – IDH+citrate – Bacillus subtilis
2uxr – DpIDH+isocitrate
1itw – AvIDH+isocitrate+Mn++
1lwd – IDH+isocitrate+Mn++ - pig
1hqs – IDH+citrate – Bacillus subtilis
=== IDH+isocitrate+NADP ===
1ide - EcIDH (mutant)+isocitrate+NADP+Mg++
1ai3 – EcIDH+isocitrate+NADP+Mg++
1ai2 – EcIDH+isocitrate+NADP+Ca++
1ai3 – EcIDH+isocitrate+NADP+Mg++
1ai2 – EcIDH+isocitrate+NADP+Ca++
1t0l – hIDH+NADP+isocitrate+Ca++
2d4v – IDH+NAD+citrate – Acidithiobacillus thiooxidans
1xkd – ApIDH+NADP+isocitrate+Ca++
2cmv – mIDH+NADP+citrate+Cd++
=== IDH+ -ketogluterate ===
1cw4 - EcIDH (mutant)+ -ketogluterate+Mn++
1ika - EcIDH+ -ketogluterate+Ca++
2qfx – yIDH+NADPH+-ketogluterate+Ca++
2qfy -  yIDH+-ketogluterate
=== IDH+ oxalosuccinate ===
1idc - EcIDH (mutant)+oxalosuccinate+Mg++
=== IDH+IDHK/P ===
3lcb – EcIDH+IDHK/P+ATP+AMP


=='''References'''==
=='''References'''==

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Michael Nobbe, Alexander Berchansky, David Canner, Michal Harel, Joel L. Sussman
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