Sandbox Reserved 1798

This Sandbox is Reserved from Mar 1 through Jun 1, 2023 for use in the course CHEM 351 Biochemistry taught by Bonnie_Hall at the Grand View University, Des Moines, USA. This reservation includes Sandbox Reserved 1796 through Sandbox Reserved 1811.

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Chorismate Dehydratase MqnA

spinqualitylabelsall models First enzyme on the futalosine pathway, proceeds via substrate assisted catalysis Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D 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 or to the article describing Jmol to the rescue. Function of your protein MqnA is found in prokaryotes and eukaryotes: some bacteria, fungi and plants that utilize the futalosine pathway or the shikimate pathway. The Chorismate Dehydratatase MqnA is an enzyme that acts upon chorismate, a biochemical intermediate in plants and microorganisms. On the futalosine pathway, it converts chorismate to EPB by removing water. MqnA is the only known chorismate dehydratase. You can see the two-part portion of the protein. The protein has been made somewhat transparent so you can see the substrate within the ligand. Two linkers connect two similar lobes. Alpha helices surround a beta-sheet. The C-terminal lobe inserts after β-strand number four on the N-terminal lobe, as many VFT proteins do. A long, 90-amino-acid-long α-clamp wraps around lobe 1’s back side. A number of hydrophobic amino acid contacts on helix α9, the loop connecting α11 and α12, and the C-terminus. There is a π-bulge on center α6 helix of the second lobe that has hydrophobic interactions between the α-clamp and α6. (Hydrophobic areas are shown in green, the rest of the molecule is in brown.) The most important amino acids in this equation is Phe73-Ala77 and Ile160 (shown in bright pink). The futalosine pathway biosynthesizes menaquinone, a carrier of electrons in electron transport chain in prokaryotes. Menaquinone is important for a number of functions in the human body, including cell growth control, apoptosis, and the metabolism of calcium, to name a few. As the human body cannot create menaquinone, it derives it from intestinal bacteria, diet, or by converting plant vitamin K1 (phylloquinone). The example we are showing is from Streptomyces coelicolor. The other mutant MqnA are from Escherichia coli. The substrate for MqnA is chorismate. It is converted to menaquinone through two different pathways, the futalosine or the o-succinyl-benzoate pathways. On the futalosine pathway, chorismate is converted to 3-enolpyruvyl-benzoate (3-EPB) by our enzyme of interest. Biological relevance and broader implications If the cell did not have MqnA, it would still be able to make menaquinone from chorismate through the —succinyl-benzoate pathway, but not through the futalosine pathway. Both of these pathways are used by bacteria, however several types of harmful bacteria, including Campylobacter jejuni, Helicobacter pylori, Chlamydiae, and spirochetes employ the futalosine pathway. The idea is that targeting the enzymes on this pathway may be a great target for some future antibiotic. Since there is no other known enzyme other than MqnA that creates 3-EPB from chorismate, (processed in the bacteria listed above,) developing an antibiotic to target this specific enzyme may be advantageous. Likewise, as MqnA processes chorismate on the shikimate pathway, and this pathway is only found in plants, bacteria, and fungi, targeting the protein may be promising target for antimicrobials and herbicides. MqnA is relevant to science in that the unique attributes of the protein, such as it’s unique placement in metabolic pathways and Venus fly-trap (VFT) unique structure give much for scientists to digest and theorize about. If the protein is a key piece of a metabolic structure, for example, destruction or inhibition of it can regulate growth of the entire organism. The mechanics of the protein is studied and compared to similar structures with the VFT in other enzymes like desulfinase DszB, thiamin pyramidine synthase The5, and thiaminase I. Ordinarily, a rigid portion of the enzyme lobe hinged with another rigid body lobe. The angle of one to the other changes as the ligand is bound and closed or unbound and open. The angle of the hinged motion is from 52 to 37 degrees. Though in other species it can be 7 degrees of motion. Different regional amino acids can make the difference in how the mechanism works. The active site of region 109 to 112 can account for the area that will make the most changes in binding if the amino acids are changed. When closed upon each other, the enzymatic mechanism is bound, conversely, when open, unbound. Important amino acids These are the important amino acids within the ligand. The active site is deep within the enzyme. Instead of positively charged side chains contacting the 3-EPB carboxylate groups, they land at the N termini of the α3 and α4 for the benzoate carboxylic group and α1 and α6 for the enol pyruvate group. The negative charges in the groups connect with positive poles on the alphahelices. The acetate ion on DrMqnA connects to strong hydrogen bonds on Asn17 and Ser86. The main amide chain is composed of Gly151. The 3-EPB benzoate carboxylic group bonds with hydrogen bonds to Thr59 and Ser109. Arg110, Thr111 and Ser112 compose the mobile loop. It is thought that 3-EPB binds and draws residues from lobe 2 to the active site. Two water molecules form hydrogen bonds with the carboxy groups on the 3-EPB. Hydrogen bonds form between enol pyruvyl group of 3-EPB during dehydration to position C3 of 3-EPB and the carboxylate oxygen O13 on the enzyme. Hydrogens consequently leave the C3 by the enol pyruvyl group. Structural highlights Here is the MqnA color by Group, and a transparent representation of the protein. Here are the alpha-helices. You can see the substrate buried deep within the enzyme. It is dehydrated by the interaction described above. The dimer is illustrated as two separate colors of the enzyme. The two sides work together in the VFT motion to form the new substrate, EPB. Here are the main secondary structures, which are, in effect, the residues that do the binding, the ligands. And here is the ligand on its own. Here are the main tertiary alpha helix A (in orange), sheets A (in dark green), and quaternary features. Namely, the alpha-helices and the dimer protein, (teal and fuchsia) as illustrated by the bi-color cartoon. Here is the space-filling view of the protein in question.