Sandbox bcce04

From Proteopedia

(Difference between revisions)

Current revision

Imaginary Protein

Mechanism

Regulation and Inhibition

3D structures of Imaginary isomerase

Additional Resources

References

↑ 2
↑ 3
↑ 4
↑ 5

Retrieved from "http://52.214.119.220/wiki/index.php/Sandbox_bcce04"

@@ Line 2: / Line 2: @@
 <StructureSection load='1iat' size='450' side='right' scene='' caption=''>
-'''Imaginaryase''' (alternatively known as '''imaginary isomerase''' or '''imaginary-8-phosphate isomerase''') are a group of enzymes of the isomerase family ([[EC]] 5.3.a.b), so named for their main function in metabolism. In this pathway imaginary isomerase (IGI) is used to inter-convert imaginary-8-phosphate and reality-6-phosphate. This reaction is driven by the relative concentrations of these molecules in the imaginary/reality matrix of the cell <ref>1</ref>.
+'''Imaginaryase''' (alternatively known as '''imaginary isomerase''' or '''imaginary-6-phosphate isomerase''') are a group of enzymes of the isomerase family ([[EC]] 5.3.a.b), so named for their main function in metabolism. In this pathway imaginary isomerase (IGI) is used to inter-convert imaginary-6-phosphate and reality-6-phosphate.
@@ Line 10: / Line 10: @@
 * Something my prof thinks is cool <ref>4</ref>.
 * Something really boring <ref>5</ref>.
-* IGI is important for metabolism in many different living organisms. <ref>5</ref>.
 =='''Structure'''==
-[[Image:Align.jpg|thumb|left|'''Figure 1.''' Multiple alignment PGI - ''Geobacillus stearothermophilus'' (white),'' Homo sapiens'' (pink), ''Oryctolagus cuniculus'' (blue)<ref>    Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE. UCSF Chimera--a visualization system for exploratory research and analysis.  J Comput Chem. 2004 Oct;25(13):1605-12. </ref>]]
-Phosphoglucose isomerase exists in the cell usually as a <scene name='Stancu_Phosphoglucoisomerase_Sandbox_1/Dimer/1'>homodimer</scene>, nevertheless outside of the cell, it has been isolated as a <scene name='Stancu_Phosphoglucoisomerase_Sandbox_1/Monomer/1'>monomeric</scene> structure. PGI has essentially an identical fold in all of the characterized species (see '''Figure 1'''). The <scene name='Stancu_Phosphoglucoisomerase_Sandbox_1/Sec_struct/1'>secondary structure</scene> of phosphoglucose isomerase is charaterized by an αβα conformation, on each of its two domains. The smaller domain is characterized by 5 parallel β-sheets, while the larger domain if formed out of 6 parallel/antiparallel β-sheets. Furthermore, another characteristic trait is a residue extension at the C-terminus, which wraps around the other monomer in the dimeric conformation. A "hook" that can potentially be involved in the previously mentioned extracellular activities.
+Imaginary isomerase exists in cells usually as a <scene name='Stancu_Phosphoglucoisomerase_Sandbox_1/Dimer/1'>homodimer</scene>, nevertheless outside of cells, it has been isolated as a <scene name='Stancu_Phosphoglucoisomerase_Sandbox_1/Monomer/1'>monomeric</scene> structure. The <scene name='Stancu_Phosphoglucoisomerase_Sandbox_1/Sec_struct/1'>secondary structure</scene> of imaginary isomerase is characterized by a conformation, on each of its two domains. Fill in the information here to give more detail.
-Phosphoglucose isomerase has a monomer molecular mass of proximately 55 kDa.
-'''Active Site''' - Mammalian PGI shows a degree of <scene name='Stancu_Phosphoglucoisomerase_Sandbox_1/Conservation2/1'>conservation</scene> ( dark red for highly conserved regions - dark blue for variable reigions) of about 90 %. The <scene name='Stancu_Phosphoglucoisomerase_Sandbox_1/Active_site2/1'>active site</scene> is the region with highest observed conservation, containing a number of residues that are crucial in the enzyme-substrate interaction mechanism (Lys210, Gln353, Glu357, Gln511, Lys518, His388b).  Lys518(His388) and Glu357 <scene name='Gilman_sandbox_1/Lys_518_and_glu_357/1'>Lys 518(His388) and Glu357 </scene>  are the main components of ring opening, while many of the other residues can be used for stabliziation and orientation.
-Another characteristic of phosphoglucose isomerase is that binding of substrate at the active site induces a small movement in the conformation of the enzyme. This can be seen in '''Figure 2''' as change in the position of an α helix.
-[[Image:Active_site_movement.jpg|thumb|left|'''Figure 2.''' Substrate induced movement]]
 </StructureSection>
 __NOTOC__
 =='''Mechanism'''==
-The proposed reaction mechanism of PGI for the reversible conversion of glucose-6-phosphate to fructose 6-phosphate involves an acid/base catalysis by the enzyme. The basic mechanism involves the isomerization of an aldose to a ketose.  This is performed by a ring opening, followed by an isomeration of the opened ring, then a ring closing.  A detailed step by step mechanism of this process can be seen as follows <ref> Voet D, Voet J, and  Pratt C. Fundamentals of Biochemistry Life at the Molecular Level. New York: John Wiley & Sons, 2008. Print.</ref>:
-'''Step 1.''' The substrate binds to the enzyme.
-'''Step 2.''' The residue Lys518 (or His388b) acts as an enzymatic acid catalyzing the opening of the ring.
-'''Step 3.''' Conserved Glu357 abstracts the acidic proton from C2 forming a cis-enendiol intermediate.
-'''Step 4.''' Glu357 donates back the proton at the C1 position.
-'''Step 5.''' Lys518 (or His388b) abstracts back the proton from the sugar ring oxygen, resulting in a ring closure, to give the product.
-[[Image:Mech.png]]
 =='''Regulation and Inhibition'''==
-'''Regulation'''  of phosphoglucoisomerase is only done by the relative concentrations of glucose-6-phosphate and fructose 6-phosphate, towards equilibrium. Nevertheless, it was found that the kinetic parameters of PGI does depend on the pH and temperature of the environment.
-The following kinetic parameters are proposed for rabbit PGI at pH 8.5 and  30°C <ref>PMID: 5647261</ref>
+==3D structures of Imaginary isomerase==
-[[Image:Kinetic_PGI.JPG]]
+==Additional Resources==
-It is interesting to point the regulation of PGI in other aspects that are not involved in metabolism.  For example, PGI acts as a "cytokine" outside the cell in that it can be used as a cell signalling protein.  PGI has been found to to be associated with AMF cells, which is found to regulate tumor cell motility.  Regulation of these extracellular "cytokine" PGI/AMF can be seen.  The amount of PGI/AMF that is secreted inside and outside the cell based on infection <ref> Funasaka T, Hu H, Yanagawa T, Hogan V, Raz A. Down-Regulation of Phosphoglucose Isomerase/Autocrine Motility Factors Results in Mesenchymal-to-Epithelial Transition of Human Lung Fibrosarcoma Cells. (2007) Cancer Res, 76(9) </ref>.
-'''Inhibition'''    of the phosphoglucoisomerase regulated reaction of glucose-6-phosphate to fructose-6-phosphate can also occur.  Competitive competition can take place from inhibitors such as 5PAH.  5PAH resembles PGI, differing only in a nitrogen atom at the first carbon position.  5PAH is reported to have a Ki of .0000002 M <ref> Arsenieva D, Hardre R, Salmon L, Jeffery CJ.  The crystal structure of rabbit phosphoglucose isomerase complex with 5-phospho-D-arabinonohydroxamic acid. (2002),PNAS, 99(9) </ref>.
-=='''Links'''==
-* Crystal Structure of human phosphoglucose isomerase (PDB=[[1iat]])
-* Crystal Structure of rabbit phosphoglucose isomerase complexed fructose 6-phosphate (PDB=[[1hox]]<ref>PMID:11425306</ref>)
-* Other available structures [[1dqr]], [[1g98]], [[1gzd]], [[1gzv]], [[1hm5]], [[1iri]], [[1jiq]], [[1jlh]], [[1koj]], [[1n8t]], [[1nuh]], [[1xtb]].
-==3D structures of phosphoglucose isomerase==
-===PGI===
-[[2pgi]], [[1b0z]] – GsPGI – ''Geobacillus stearothermophilus''<br />
-[[1dqr]], [[1hm5]], [[1n8t]] – rPGI – rabbit<br />
-[[1iat]], [[1jlh]] – hPGI – human<br />
-[[1qxj]], [[1x8e]], [[3sxw]] – PfPGI – ''Pyrococcus furiosus''<br />
-[[1j3p]], [[1j3q]] – TlPGI – ''Thermococcus litoralis''<br />
-[[1q50]] – LmPGI – ''Leishmania Mexicana''<br />
-[[1u0e]], [[2cvp]] – mPGI – mouse<br />
-[[2q8n]] – PGI – ''Thermotoga maritima''<br />
-[[3hjb]] – PGI – ''Vibrio cholera''<br />
-[[3ifs]] – PGI – ''Bacillus anthracis''<br />
-[[2wu8]] – PGI – ''Mycobacterium tuberculosis''<br />
-[[3ljk]] – FtPGI (mutant) – ''Francisella tularensis''<br />
-[[3nbu]] – PGI – ''Escherichia coli''
-===PGI complex with fructose-6-phosphate===
-[[1hox]] – rPGI + fructose-6-phosphate<br />
-[[1t10]] - LmPGI + fructose-6-phosphate<br />
-[[2gc2]] - PfPGI + fructose-6-phosphate<br />
-[[2cxs]], [[2cxt]] - mPGI + fructose-6-phosphate<br />
-[[3m5p]] - FtPGI (mutant) + fructose-6-phosphate<br />
-===PGI complex with sorbitol-6-phosphate===
-[[1xtb]] - rPGI + sorbitol-6-phosphate<br />
-[[2gc1]] - PfPGI + sorbitol-6-phosphate<br />
-[[2cxq]] - mPGI + sorbitol-6-phosphate<br />
-===PGI complex with phosphoarabinose===
-[[1gzd]], [[1gzv]] – PGI + phosphoarabinose – pig<br />
-[[1c7r]] - GsPGI + phosphoarabinose<br />
-[[2cxp]] – mPGI + phosphoarabinose<br />
-[[1nuh]] - hPGI + phosphoarabinose<br />
-[[1qsr]], [[1x7n]], [[1x82]] - PfPGI + phosphoarabinose<br />
-[[2gc0]] - PfPGI + phosphoarabinose derivative<br />
-[[1koj]] – rPGI + phosphoarabinose derivative
-===PGI complex with gluconate-6-phosphate===
-[[1qy4]] - PfPGI + gluconate-6-phosphate<br />
-[[1j3r]] - TlPGI + gluconate-6-phosphate<br />
-[[2cxr]] - mPGI + gluconate-6-phosphate<br />
-[[3q7i]] - FtPGI (mutant) + gluconate-6-phosphate<br />
-===PGI complex with glucose-6-phosphate===
-[[1u0f]] - mPGI + glucose-6-phosphate<br />
-[[3ff1]] - PGI + glucose-6-phosphate – ''Staphylococcus aureus''<br />
-[[2o2c]] - TbPGI + glucose-6-phosphate – ''Trypanosoma brucei''
-===Other PGI binary complexes===
-[[2o2d]] – TbPGI + citrate<br />
-[[1u0g]], [[2cxo]] - mPGI + erythrose-4-phosphate<br />
-[[3q88]] – FtPGI (mutant) + ribose bisphosphate<br />
-[[1c7q]] – GsPGI + phosphate inhibitor<br />
-[[2cxn]], [[2cxu]] – mPGI + phosphate<br />
-[[1g98]] – rPGI + transition state analog<br />
-[[2gc3]] - PfPGI + mannose-6-phosphate<br />
-==Additional Resources==
-For additional information, see: [[Carbohydrate Metabolism]]
-<br />
 ==References==
 <references/>

Sandbox bcce04

From Proteopedia

Current revision

Imaginary Protein

Structure

Mechanism

Regulation and Inhibition

3D structures of Imaginary isomerase

Additional Resources

References

Views

Personal tools

Navigation

Search

Toolbox