Sandbox Reserved 1057: Difference between revisions

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OCA, Sydney Pate, Perry Rabin, Geoffrey C. Hoops, Natalie Van Ochten

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-'''Bold text'''=='''Isocitrate Lyase from ''Mycobacterium tuberculosis'''''==
+{{Sandbox_Reserved_Butler_CH462_Sp2015_#}}<!-- PLEASE ADD YOUR CONTENT BELOW HERE -->
-===Wild Type Protein===
+==Your Protein Name here==
-===3-Bromopyruvate===
+<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>
-===3-Nitropropionate===
+This is a default text for your page ''''''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.
-<StructureSection load='1f8I' size='340' side='right' caption='Isocitrate Lyase' scene=''>
-This is a default text for your page '''Sydney Pate/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.
 You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.
-== Structure ==
+== Biological Function ==
-[[Image:Normal_Crystal_Structure.png|300 px|center|thumb|Figure Legend]]
+== Structural Overview ==
-<ref name="sharma"> Sharma, V.; Sharma, S.; Hoener zu Bentrup, K.; McKinney, J.; Russell, D.; ''et. al''; Structure of isocitrate lyase, a persistence factor of ''Mycobacterium tuberculosis''. ''Nat. Struct. Biol.''. '''2000'''. ''7(8)'':663-668. </ref>
+== Mechanism of Action ==
-<ref name="gould"> Gould, T.; van de Langemheen, H.; Muñoz-Elías, E.; McKinney, D.; Sacchettini, J.; Dual role of isocitrate lyase 1 in the glyoxylate and methylcitrate cycles in ''Mycobacterium tuberculosis''. ''Molecular Microbiology''. '''2006'''. ''61(4)'':940-947. doi:10.1111/j.1365-2958.2006.05297.x. </ref>
+== Zinc Ligand(s) ==
-The active site of isocitrate lyase consists of eight residues: Trp93, Cys191, His193, Ser315, Ser317, Asn313, Thr347, Leu348. Additionally, there are several other amino acid side chains present that form hydrogen bonding opportunities with isocitrate to catalyze the breakdown reaction to glyoxylate and succinate. Ser91, Gly92, Trp93, and Arg228 form hydrogen bonds with glyoxylate while Asn313, Glu295, Arg228, and Gly192 and Trp93, Thr347, Ser315, Ser317, and His193 form hydrogen bonding opportunities with the two carboxylates within succinate. <ref name="sharma"> Sharma, V.; Sharma, S.; Hoener zu Bentrup, K.; McKinney, J.; Russell, D.; ''et. al''; Structure of isocitrate lyase, a persistence factor of ''Mycobacterium tuberculosis''. ''Nat. Struct. Biol.''. '''2000'''. ''7(8)'':663-668. </ref> Additionally, a Mg<sup>2+</sup> ion is needed for further electrostatic stabilization of the extreme negative charge on isocitrate. This Mg<sup>2+</sup> hydrogen bonds to the carboxylate in glyoxylate and one of the carboxylates in succinate.
+== Other Ligands ==
-The catalytic loop of isocitrate lyase consists of residues 185-196. The two most important are Cys191 and His193 as these form a charge relay strong enough to extract a proton from isocitrate. Poor electron density has been observed for residues His193 and Leu194 indicating that this loop is very flexible. <ref name="sharma"> Sharma, V.; Sharma, S.; Hoener zu Bentrup, K.; McKinney, J.; Russell, D.; ''et. al''; Structure of isocitrate lyase, a persistence factor of ''Mycobacterium tuberculosis''. ''Nat. Struct. Biol.''. '''2000'''. ''7(8)'':663-668. </ref> This data backs up the claim that that monomers of the protein are in a structural equilibria between the open and closed forms of the active site. In order for the catalytic loop to shift into the closed position necessary for catalysis, isocitrate must be within the binding pocket. The hydrogen bonding opportunities formed cause a ripple effect that shifts the catalytic loop into a closer position. <ref name="sharma"> Sharma, V.; Sharma, S.; Hoener zu Bentrup, K.; McKinney, J.; Russell, D.; ''et. al''; Structure of isocitrate lyase, a persistence factor of ''Mycobacterium tuberculosis''. ''Nat. Struct. Biol.''. '''2000'''. ''7(8)'':663-668. </ref> This shift also causes the C-terminal domain of the subunit (residues 411-428) to move into the former position of the catalytic loop. The C-terminal domain is stabilized by an electrostatic interaction with Lys189. This combined movement locks the active site residues into a proper orientation for lysis of a C-C bond within isocitrate. <ref name="sharma"> Sharma, V.; Sharma, S.; Hoener zu Bentrup, K.; McKinney, J.; Russell, D.; ''et. al''; Structure of isocitrate lyase, a persistence factor of ''Mycobacterium tuberculosis''. ''Nat. Struct. Biol.''. '''2000'''. ''7(8)'':663-668. </ref>
-<scene name='69/694224/Succinate_hydrogen_bonding/1'>succinate hydrogen bonding</scene>
-== Function ==
-<scene name='69/696877/Residues_close_to_active_site/2'>(Residues_close_to_active_site)</scene>
-<scene name='69/696877/Residues_close_to_active_site/3'>(You_OKd_This)</scene>
-== Disease ==
-== Relevance ==
-The thiol group on the conserved Cys191 gets deprotonated by His193 residue to make it a better nucleophile that will deprotonate the alcohol on isocitrate.
-Mg<sup>2+</sup> is used to stabalize the electrostatic repulsion of two of the three negative charges of the carboxylates.  The oxyanion resonates to break a C-C bond forming two products and to force a carbonyl into an oxyanion. On this second product, the oxyanion resonates to form two carboxylates that are stabalized by a Mg ion.
-== Structural highlights ==
 This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.