Sandbox Reserved 1058: Difference between revisions

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===Catalytic Loop===

[[Image:Active Loop Shift.png|250 px|left|thumb|'''Figure 5. Active Site Loop Shift.''' Binding of the ligand to the enzyme results in a conformational shift that facilitates the breakdown of isocitrate. The active site loop unbound is shown in wheat and the active site loop bound is shown in green.]] The catalytic loop of isocitrate lyase consists of residues 185-196 (Figure 5). 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 <scene name='69/694225/C-terminus_loop_in_cat_loop/1'>move into the former position of the catalytic loop (in green)</scene>. 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>

[[Image:Active Loop Shift.png|250 px|left|thumb|'''Figure 5. Active Site Loop Shift.''' Binding of the ligand to the enzyme results in a conformational shift that facilitates the breakdown of isocitrate. The active site loop unbound is shown in wheat and the active site loop bound is shown in green.]] The catalytic loop of isocitrate lyase consists of residues 185-196 (Figure 5). 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 <scene name='69/694225/C-terminus_loop_in_cat_loop/1'>move into the former position of the catalytic loop (in green)</scene>. The C-terminal domain is stabilized by an <scene name='69/694225/Lys_electrostatic/1'>electrostatic interaction</scene> 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>

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Revision as of 05:23, 10 April 2015 view source Sydney Pate (talk \| contribs) 44 edits No edit summary ← Older edit		Revision as of 05:26, 10 April 2015 view source Sydney Pate (talk \| contribs) 44 edits No edit summary Newer edit →
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	===Catalytic Loop===		===Catalytic Loop===
	[[Image:Active Loop Shift.png\|250 px\|left\|thumb\|'''Figure 5. Active Site Loop Shift.''' Binding of the ligand to the enzyme results in a conformational shift that facilitates the breakdown of isocitrate. The active site loop unbound is shown in wheat and the active site loop bound is shown in green.]] The catalytic loop of isocitrate lyase consists of residues 185-196 (Figure 5). 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 <scene name='69/694225/C-terminus_loop_in_cat_loop/1'>move into the former position of the catalytic loop (in green)</scene>. 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>		[[Image:Active Loop Shift.png\|250 px\|left\|thumb\|'''Figure 5. Active Site Loop Shift.''' Binding of the ligand to the enzyme results in a conformational shift that facilitates the breakdown of isocitrate. The active site loop unbound is shown in wheat and the active site loop bound is shown in green.]] The catalytic loop of isocitrate lyase consists of residues 185-196 (Figure 5). 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 <scene name='69/694225/C-terminus_loop_in_cat_loop/1'>move into the former position of the catalytic loop (in green)</scene>. The C-terminal domain is stabilized by an <scene name='69/694225/Lys_electrostatic/1'>electrostatic interaction</scene> 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>