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| {{Sandbox_Reserved_Butler_CH462_Sp2015_#}}<!-- PLEASE ADD YOUR CONTENT BELOW HERE --> | | {{Sandbox_Reserved_Butler_CH462_Sp2015_#}}<!-- PLEASE ADD YOUR CONTENT BELOW HERE --> |
| ==''Mycobacterium tuberculosis'' Catalase-Peroxidase== | | ==Your Protein Name here== |
| | <StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''> |
| | This is a default text for your page ''''''. Click above on '''edit this page''' to modify. Be careful with the < and > 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. |
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| '''ELLIE'S SANDBOX IS THE REAL DEAL'''
| | == Biological Function == |
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| <StructureSection load='1SJ2' size='340' side='right' caption='Caption for this structure' scene=''>
| | == Structural Overview == |
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| | == Mechanism of Action == |
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| == Function == | | == Zinc Ligand(s) == |
| Β | |
| == Disease ==
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| Β | |
| == Relevance ==
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| Β | |
| == Structural highlights ==
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| Β | |
| <scene name='69/694238/Homodimer/1'>homodimer</scene>
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| Β | |
| <scene name='69/694238/N_terminus/5'>N terminus</scene>
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| Β | |
| <scene name='69/694238/N_terminus/6'>N terminus stabilization with residues</scene>
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| Β | |
| Β | |
| <scene name='69/694238/Active_site/3'>Arg 104, Trp 107, His 108, His 270, Asp 381</scene>
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| Β | |
| <scene name='69/694238/Active_site/5'>binding site</scene>
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| Β | |
| <scene name='69/694238/Active_site/6'>Asp 137</scene>
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| Β | |
| <scene name='69/694238/Active_site/7'>Ser 315</scene>
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| Β | |
| <scene name='69/694238/Active_site/8'>His 108</scene>
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| Β | |
| Β | |
| Β | |
| Β | |
| blue - n terminus hook
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| magenta - n terminus
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| light pink - c terminus
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| Β | |
| Β | |
| Β | |
| <scene name='69/694238/N_terminus/2'>hook</scene>
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| Β | |
| [[Image:INH.png|300 px|left|thumb|Figure Legend]]
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| Β | |
| There are 6 conserved key active site residues that suround the <scene name='69/694238/Heme/2'>heme</scene>.Β These <scene name='69/694238/Active_site/2'>active site</scene> residues are Arg 104, Trp 107, His 108, His 270, Asp 381.
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| Β | |
| [[Image:INH_mechanism.PNG|300 px|left|thumb|Figure Legend]]
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| Β | |
| The location of the binding site forΒ [http://en.wikipedia.org/wiki/Isoniazid isoniazid (INH)] is located near the ''Ξ΄ meso'' heme edge, about 3.8 Γ
away from the heme iron. This binding site is found within what is considered to be the usual substrate access channel of peroxidases.Β The reaction between INH and the enzyme must occur from interaction in a binding site intended for the natural substrate (A2).Β Asp 137 plays a key role in the activation and binding of INH.Β Asp 137 creates energetically favorable interactions due to its ability to make hydrogen-bond interactions between its carboxylic acid side chain and the pyridinyl N1 of INH.Β
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| Β | |
| [[Image:INH_structure._PNG.PNG|300 px|left|thumb|Chemical Structure of Isoniazid (INH)]]
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| Β | |
| There are many possible mutations in this peroxidase that can play a role in the resistance of INH.Β The most commonly occurring mutation occurs at Ser 315. A mutation at this amino acid can result in up to a 200 fold increase in the minimum inhibitory concentration for INH.Β Ser 315 has been reported to mutate to asparagine, isoleucine, glycine, and most frequently, threonine.Β A S315T mutant has the ability to reduce the affinity of the enzyme for INH by increasing steric hindrance and reducing access to the substrate binding site.Β Any of the other mutations at this site, except for glycine, would also increase steric hindrance and decrease the accessibility to the binding site.
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| Of the active site residues that are involved in enzyme catalyzed activation of INH, only His 108 has been a site for mutations that can increase resistance to INH. His 108 has been reported to mutate to glutamic acid and glutamine. These mutations reduce the affinity for INH but the hydrogen bond donor/acceptor groups of glutamine would still allow INH to bind.Β However, glutamine wouldn't be able to act as proton shuttle in the way His 108 does in the enzyme-catalyzed activation pathway.Β
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| Β | |
| No known mutants have been reported to occur at Asp 137, although a few mutants nearby could cause local conformational changes and thereby altering the orientation of the Asp 137 side chain, making it less effective in binding and activation of INH.Β
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| Β | |
| [[Image:Mutation_locations.png|300 px|left|thumb|Pink residues represent the location of possible mutations.Β Green residues represent the active site. Asp 137 is shown in blue.]]
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| Β | |
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| | == Other Ligands == |
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| 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. | | 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. |