Sandbox Reserved 1071

This Sandbox is Reserved from 02/09/2015, through 05/31/2016 for use in the course "CH462: Biochemistry 2" taught by Geoffrey C. Hoops at the Butler University. This reservation includes Sandbox Reserved 1051 through Sandbox Reserved 1080.

To get started: Click the edit this page tab at the top. Save the page after each step, then edit it again. Click the 3D button (when editing, above the wikitext box) to insert Jmol. show the Scene authoring tools, create a molecular scene, and save it. Copy the green link into the page. Add a description of your scene. Use the buttons above the wikitext box for bold, italics, links, headlines, etc. More help: Help:Editing

Mycobacterium tuberculosis Catalase-PeroxidaseMycobacterium tuberculosis Catalase-Peroxidase

ELLIE'S SANDBOX IS THE REAL DEAL

Structural highlights blue - n terminus hook magenta - n terminus light pink - c terminus Figure Legend There are 6 conserved key active site residues that suround the . These residues are Arg 104, Trp 107, His 108, His 270, Asp 381. Figure Legend The location of the binding site for isoniazid (INH) is located near the δ meso heme edge, about 3.8 Å away from the heme iron. This binding site is found within what is considered to be the usual substrate access channel of peroxidases. The reaction between INH and the enzyme must occur from interaction in a binding site intended for the natural substrate (A2). Asp 137 plays a key role in the activation and binding of INH. 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. Chemical Structure of Isoniazid (INH) There are many possible mutations in this peroxidase that can play a role in the resistance of INH. 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. Ser 315 has been reported to mutate to asparagine, isoleucine, glycine, and most frequently, threonine. 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. Any of the other mutations at this site, except for glycine, would also increase steric hindrance and decrease the accessibility to the binding site. 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. However, glutamine wouldn't be able to act as proton shuttle in the way His 108 does in the enzyme-catalyzed activation pathway. 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. Pink residues represent the location of possible mutations. Green residues represent the active site. Asp 137 is shown in blue. This is a sample scene created with SAT to by Group, and another to make of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

spinqualitylabelsall models Caption for this structure Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image