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| - | {{Sandbox_Reserved_Butler_CH462_Sp2015_#}}<!-- PLEASE ADD YOUR CONTENT BELOW HERE --> | + | *[[User:Jessica Klingensmith/Sandbox1]]{{Sandbox_Reserved_Butler_CH462_Sp2015_#}}<!-- PLEASE ADD YOUR CONTENT BELOW HERE --> |
| - | ==''Mycobacterium tuberculosis'' salicylate synthase (Mbt1)== | + | ==''ZN Ion Transporter YiiP found in E.Coli''== |
| - | <StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>
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| - | This is a default text for your page ''''''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
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| - | 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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| - | ==Introduction== | + | |
| - | ''Mycobacterim tuberculosis'' salicylate synthase (MtbI) is a highly promiscuous enzyme that has four distinct activities: isochorismate synthase (IS), isochorismate pyruvate lyase (IPL), salicylate synthase (SS) and chromate mutate (CM). MtbI belongs to the MST enzyme family, which consists of structural homologues (Irp9, MenF, EntC, and MtbI) that isomerize chromate to isochorismate. These enzymes are in involved in menaquinone, siderophore, or tryptophan biosynthesis.
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| - | ==Structure== | + | <StructureSection load='3H90' size='350' side='right' caption='ZN Ion Transporter YiiP' scene='White residues'> |
| - | The crystal asymmetric unit was found to contain <scene name='69/694235/3log/1'> four MbtI molecules</scene>, however crystal packing and size exclusion chromatography data suggest a monomeric enzyme. There are no significant structural changes between the four monomers excepts from the localized differences in the active site. The overall molecular structure consist of a polypeptide of 450 residues that forms one large single domain with a similar fold to other chromate-utilizing enzymes. The core of the protein is formed by 21 beta-strands folded into a twisted beta-sandwich. The protein's core is then surrounded by 10 alpha helices.
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| | + | This is a default text for your page, Here is my image! [[Image:3h90.0_chimera_tm_350_350.png |100px|left|thumb|Figure Legend]] ''''''. 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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| - | == Disease == | |
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| - | Mycobacterium tuberculosis is the causative agent of Tuberculosis (TB), an infectious disease that affects one-third of the worlds population. Iron is essential for mycobacterial growth and pathogenesis
| + | == Biological Function == |
| - | The salicylate synthase activity of MbtI produces salicylate from chorismate through an isochorismate intermediate. This reaction is Mg dependent. Chorismate is then used in the biosyntheses of Mycobactin T, the siderophore of ''M. tuberculosis''. The siderophore sequesters iron, covering pathogenesis of'' M. tuberculosis''.
| + | <scene name='69/694235/White_residues/1'>zoom of white residues</scene> and also this view: |
| | + | <scene name='69/694235/White_residues2/1'>alternate angle</scene> |
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| - | == Function == | + | === SubHeading 1 === |
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| - | == Relevance == | + | == Structural Overview == |
| | + | === Subheading 2 === |
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| | + | == Mechanism of Action == |
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| - | == Structural highlights == | + | == Zinc Ligand(s) == |
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| - | ==Mechanism== | + | == Other Ligands == |
| - | A magnesium ion in the active site orients the C1 carboxyl group of chorismate. A lysine residue then serves as a general base for the activation of a water molecule to attack at C2
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| - | The catalytic mechanism for conversion of isochorismate to salicylate by MbtI is a sigmatropic, pericyclic mechanism that is pH-dependent. Chromate mutase activity is only observed in the absence of magnesium ion in the active site while salicylate synthase activity is depended on magnesium ion. The active site of MbtI is altered by the removal of the magnesium cofactor causing chromate mutase activity. MbtI has differing binding modes for chromate that leads to different substrate conformations/transition states and resulting in different products.
| + | <scene name='69/694235/Asp49/1'>Asp49</scene> |
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| - | ==Inhibition Studies== | |
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| | + | <scene name='69/694235/His153/1'>His153</scene> |
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| | + | <scene name='69/694235/Asp153/2'>Asp157</scene> |
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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. |
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| | </StructureSection> | | </StructureSection> |
| | == References == | | == References == |
| - | | + | <references/> |
| - | 1. Chi G1, Manos-Turvey A, O'Connor PD, Johnston JM, Evans GL, Baker EN, Payne RJ, Lott JS, Bulloch EM. 2012. Implications of binding mode and active site flexibility for inhibitor potency against the salicylate synthase from Mycobacterium tuberculosis. Biochemistry 51(24):4868-79. doi: 10.1021/bi3002067
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| - | 2. Ferrer S1, Martí S, Moliner V, Tuñón I, Bertrán J. 2012 Understanding the different activities of highly promiscuous MbtI by computational methods. Phys Chem Chem Phys. 14(10):3482-9. doi: 10.1039/c2cp23149b.
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| - | 3. Harrison AJ1, Yu M, Gårdenborg T, Middleditch M, Ramsay RJ, Baker EN, Lott JS. 2006. The structure of MbtI from Mycobacterium tuberculosis, the first enzyme in the biosynthesis of the siderophore mycobactin, reveals it to be a salicylate synthase. J Bacteriol. 188(17):6081-91.
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| - | 4. Manos-Turvey A1, Cergol KM, Salam NK, Bulloch EM, Chi G, Pang A, Britton WJ, West NP, Baker EN, Lott JS, Payne RJ. 2012. Synthesis and evaluation of M. tuberculosis salicylate synthase (MbtI) inhibitors designed to probe plasticity in the active site. Org Biomol Chem 10(46):9223-36. doi: 10.1039/c2ob26736e.
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| - | 5. Zwahlen J1, Kolappan S, Zhou R, Kisker C, Tonge PJ. 2007. Structure and mechanism of MbtI, the salicylate synthase from Mycobacterium tuberculosis. Biochemistry. 46(4):954-64.
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