Sandbox Reserved 110

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<StructureSection load='6OYH' size='340' side='right' caption='Aricept bound to AChE' scene=''>
<StructureSection load='6OYH' size='340' side='right' caption='Aricept bound to AChE' scene=''>
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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 ==
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'''MraY''', called also '''phospho-N-acetylmuramoyl-pentapeptide-transferase''' or '''UDP-MurNAc-pentapeptide phosphotransferase''', is an integral membrane enzyme involved in peptidoglycan biosynthesis <ref name="one">PMID:29778697</ref> <ref name="two">PMID:27511599</ref>.MraY is encoded by the mraY gene and belongs to a subfamily of the polyprenyl-phosphate N-acetyl hexosamine 1-phosphate transferase (PNPT) superfamily <ref name="three">PMID:23990562</ref>. MRAY is a promising candidate for the development of new antibiotics. In fact, it is the target of five classes of natural nucleoside inhibitors with potent antibacterial activity <ref name="two"/> <ref name="four">PMID:29438582</ref>.
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dede <ref name="one">PMID:29778697</ref>. dedede dedede <ref name="one" />
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The structure presented in this page correspond to the MraY protein isolated from ''Aquifex aeolicus'' (strain VF5) in complex with carbacaprazamycin
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== Introduction ==
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<scene name='61/612822/Aricept_docks_on_tcache/1'>Aricept docked onto AChE</scene>
<scene name='61/612822/Aricept_docks_on_tcache/1'>Aricept docked onto AChE</scene>
== Function ==
== Function ==
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MraY is a critical enzyme in peptidoglycan biosynthesis. Peptidoglycan is an essential component of the cell wall of Gramnegative and Gram-positive bacteria <ref name="five">DOI:10.1039/b816215h</ref>. The cell wall provides bacteria a structural support and protection. In particular, it allows bacteria to maintain their cell shape at different osmotic pressures <ref name="six">PMID:26370936</ref>. Peptidoglycan is a cross-linked polymer of carbohydrates an amino acids and due to its biological relevance in Bacteria, it has been a major target for antibiotics <ref name="three"/> <ref name="five"/>.
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Peptidoglycan biosynthesis involves three main stages. MraY is responsible for the second stage. First, the peptidoglycan precursor UDP-Nacetylmuramoyl (MurNAc)–pentapeptide is synthesized in the cytosol. Second, this hydrophilic precursor is attached to a lipid carrier, and the complex lipid carrier-precursor is transported, through the membrane, to the periplasm. Third, the peptidoglycan precursors are polymerized to form the cell wall. MraY catalyzes the transfer of phospho-MurNAc-pentapeptide from hydrophilic substrate UDP-MurNAc-pentapeptide to the lipid carier (C55-P) in the presence of a Mg2+ cofactor. The product is the undecaprenyl-pyrophosphoryl-MurNAcpentapeptide, also known as lipid I <ref name="three"/> <ref name="seven">PMID:31266949</ref> <ref name="eight">PMID:18081839</ref>.
== Structure ==
== Structure ==
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== 3D related structure ==
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== 3D related structures ==
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.

Revision as of 01:46, 15 January 2020

This Sandbox is Reserved from May 18 through July 31, 2015 for use in the workshop Protein 3D Structure Visualization & Structural Bioinformatics taught by Eric Martz and Fadel Samatey at the Okinawa Institute of Science and Technology, Japan. This reservation includes Sandbox Reserved 101 through Sandbox Reserved 150. See Workshops.MolviZ.Org.
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

Crystal structure of MraY bound to carbacaprazamycin

Aricept bound to AChE

Drag the structure with the mouse to rotate

References

  1. ↑ Hering J, Dunevall E, Ek M, Branden G. Structural basis for selective inhibition of antibacterial target MraY, a membrane-bound enzyme involved in peptidoglycan synthesis. Drug Discov Today. 2018 Jul;23(7):1426-1435. doi: 10.1016/j.drudis.2018.05.020., Epub 2018 May 18. PMID:29778697 doi:http://dx.doi.org/10.1016/j.drudis.2018.05.020
  2. ↑ 2.0 2.1 Koppermann S, Ducho C. Natural Products at Work: Structural Insights into Inhibition of the Bacterial Membrane Protein MraY. Angew Chem Int Ed Engl. 2016 Sep 19;55(39):11722-4. doi: 10.1002/anie.201606396. , Epub 2016 Aug 11. PMID:27511599 doi:http://dx.doi.org/10.1002/anie.201606396
  3. ↑ 3.0 3.1 3.2 Chung BC, Zhao J, Gillespie RA, Kwon DY, Guan Z, Hong J, Zhou P, Lee SY. Crystal structure of MraY, an essential membrane enzyme for bacterial cell wall synthesis. Science. 2013 Aug 30;341(6149):1012-6. doi: 10.1126/science.1236501. PMID:23990562 doi:10.1126/science.1236501
  4. ↑ Koppermann S, Cui Z, Fischer PD, Wang X, Ludwig J, Thorson JS, Van Lanen SG, Ducho C. Insights into the Target Interaction of Naturally Occurring Muraymycin Nucleoside Antibiotics. ChemMedChem. 2018 Apr 23;13(8):779-784. doi: 10.1002/cmdc.201700793. Epub 2018, Mar 23. PMID:29438582 doi:http://dx.doi.org/10.1002/cmdc.201700793
  5. ↑ 5.0 5.1 Winn M, Goss RJ, Kimura K, Bugg TD. Antimicrobial nucleoside antibiotics targeting cell wall assembly: recent advances in structure-function studies and nucleoside biosynthesis. Nat Prod Rep. 2010 Feb;27(2):279-304. doi: 10.1039/b816215h. Epub 2009 Dec 16. PMID:20111805 doi:http://dx.doi.org/10.1039/b816215h
  6. ↑ Romaniuk JA, Cegelski L. Bacterial cell wall composition and the influence of antibiotics by cell-wall and whole-cell NMR. Philos Trans R Soc Lond B Biol Sci. 2015 Oct 5;370(1679). pii: rstb.2015.0024., doi: 10.1098/rstb.2015.0024. PMID:26370936 doi:http://dx.doi.org/10.1098/rstb.2015.0024
  7. ↑ Mashalidis EH, Kaeser B, Terasawa Y, Katsuyama A, Kwon DY, Lee K, Hong J, Ichikawa S, Lee SY. Chemical logic of MraY inhibition by antibacterial nucleoside natural products. Nat Commun. 2019 Jul 2;10(1):2917. doi: 10.1038/s41467-019-10957-9. PMID:31266949 doi:http://dx.doi.org/10.1038/s41467-019-10957-9
  8. ↑ Bouhss A, Trunkfield AE, Bugg TD, Mengin-Lecreulx D. The biosynthesis of peptidoglycan lipid-linked intermediates. FEMS Microbiol Rev. 2008 Mar;32(2):208-33. doi: 10.1111/j.1574-6976.2007.00089.x., Epub 2007 Dec 10. PMID:18081839 doi:http://dx.doi.org/10.1111/j.1574-6976.2007.00089.x
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