Sandbox Reserved 1556

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== Structural highlights and structure-function relationships ==
== Structural highlights and structure-function relationships ==
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GfTNMT was co-crystallized with the cofactor S-adenosyl-L-methionine (dmin = 1.6 A), product S-adenosyl-L-homocysteine (dmin = 1.8 A), or in complex with S-adenosyl-L-homocysteine and (S)-cis-N-methylstylopine (dmin = 1.8 A), These structures reveal for the first time how a mostly hydrophobic L-shaped substrate recognition pocket selects for the (S)-cis configuration of the two central six-membered rings in protoberberine BIA compounds.
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GfTNMT was co-crystallized with the cofactor S-adenosyl-L-methionine (dmin = 1.6 A), product S-adenosyl-L-homocysteine (dmin = 1.8 A), or in complex with S-adenosyl-L-homocysteine and (S)-cis-N-methylstylopine (dmin = 1.8 A), These structures reveal for the first time how a mostly hydrophobic L-shaped substrate recognition pocket selects for the (S)-cis configuration of the two central six-membered rings in protoberberine BIA compounds. The substrate specificity of TNMT enzymes appears to arise from the arrangement of subgroup-specific stereospecific recognition elements relative to catalytic elements that are more widely conserved among all BIA NMTs. The binding mode of protoberberine compounds to GfTNMT appears to be similar to coclaurine NMT, with the isoquinoline rings buried deepest in the binding pocket. This binding mode differs from that of pavine NMT, in which the benzyl ring is bound more deeply than the isoquinoline rings. The insights into substrate recognition and catalysis provided here form a sound basis for the rational engineering of NMT enzymes for chemoenzymatic synthesis and metabolic engineering.
== Energy Transformation ==
== Energy Transformation ==

Revision as of 03:10, 30 November 2019

This Sandbox is Reserved from Aug 26 through Dec 12, 2019 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 1556 through Sandbox Reserved 1575.
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Tetrahydroprotoberberine N-methyltransferase

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References

  1. Hanson, R. M., Prilusky, J., Renjian, Z., Nakane, T. and Sussman, J. L. (2013), JSmol and the Next-Generation Web-Based Representation of 3D Molecular Structure as Applied to Proteopedia. Isr. J. Chem., 53:207-216. doi:http://dx.doi.org/10.1002/ijch.201300024
  2. Herraez A. Biomolecules in the computer: Jmol to the rescue. Biochem Mol Biol Educ. 2006 Jul;34(4):255-61. doi: 10.1002/bmb.2006.494034042644. PMID:21638687 doi:10.1002/bmb.2006.494034042644
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