Revision as of 16:46, 9 April 2019

LSD Demethylase

This is a default text for your page Steve Klimcak/Sandbox 1. 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 ^[1] or to the article describing Jmol ^[2] to the rescue.

Introduction

Structure

domains

This is the tower domain

Active Site

H20phobic Pocket

Function

Mechanism

The methylation of lysine via LSD1 occurs through a 2 electron process. Shown in Figure 3 the first step involves the Flavin Adenine Dinucleotide cofactor initiating a hydride transfer from the one of the two methyl groups bound to the nitrogen at the lysine tail, via a N5 on the flavin group. An imine cation is then formed at the end of the lysine tail to compensate for the loss of hydride. In the next step the imine is hydrolyzed and transitions to an Hemiaminal. This then breaks down easily to formaldehyde and the product lysine.

Hydrophobic Pocket

The hydrophobic pocket located in the active site cavity of LSD1, forms a catalytic chamber where the substrate lysine is oriented and positioned to interact with the FAD co-factor to initiate demethylation. The specific residues making up the pocket include valine-317, glycine-330, alanine-331, methionine 332, valine-333, phenylalanine-338, leucine-569, asparagine-660, lysine-661, tryptophan 695, serine 749, serine 760, and tyrosine-761. The hydrophobic pocket shown in green surrounds the FAD in a way such that it exposes the catalytic nitrogen(N5) that is responsible for the two electron demethylation. Another three seperate pockets help bind the histone tail residues to the substrate lysine which is essential for identifying different modifications of the histone tail.

Application

Disease

Relevance

Structural highlights

This is a sample scene created with SAT to color by Group, and another to make a transparent representation of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

↑ 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:https://dx.doi.org/10.1002/ijch.201300024
↑ 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

References

^[1] ^[2]

↑ Ransey E, Paredes E, Dey SK, Das SR, Heroux A, Macbeth MR. Crystal structure of the Entamoeba histolytica RNA lariat debranching enzyme EhDbr1 reveals a catalytic Zn(2+) /Mn(2+) heterobinucleation. FEBS Lett. 2017 Jul;591(13):2003-2010. doi: 10.1002/1873-3468.12677. Epub 2017, Jun 14. PMID:28504306 doi:https://dx.doi.org/10.1002/1873-3468.12677
↑ Khalid MF, Damha MJ, Shuman S, Schwer B. Structure-function analysis of yeast RNA debranching enzyme (Dbr1), a manganese-dependent phosphodiesterase. Nucleic Acids Res. 2005 Nov 7;33(19):6349-60. doi: 10.1093/nar/gki934. Print, 2005. PMID:16275784 doi:https://dx.doi.org/10.1093/nar/gki934

Proteopedia Page Contributors and Editors (what is this?)

Steve Klimcak

[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:https://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

[”Ransey”-1] Ransey E, Paredes E, Dey SK, Das SR, Heroux A, Macbeth MR. Crystal structure of the Entamoeba histolytica RNA lariat debranching enzyme EhDbr1 reveals a catalytic Zn(2+) /Mn(2+) heterobinucleation. FEBS Lett. 2017 Jul;591(13):2003-2010. doi: 10.1002/1873-3468.12677. Epub 2017, Jun 14. PMID:28504306 doi:https://dx.doi.org/10.1002/1873-3468.12677

[Khalid-2] Khalid MF, Damha MJ, Shuman S, Schwer B. Structure-function analysis of yeast RNA debranching enzyme (Dbr1), a manganese-dependent phosphodiesterase. Nucleic Acids Res. 2005 Nov 7;33(19):6349-60. doi: 10.1093/nar/gki934. Print, 2005. PMID:16275784 doi:https://dx.doi.org/10.1093/nar/gki934

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@@ Line 12: / Line 12: @@
 == Function ==
 ===Mechanism===
-The methylation of lysine via LSD1 occurs through a 2 electron process. In the first step the <scene name='81/811710/Fad_highlight/1'>Flavin Adenine Dinucleotide cofactor</scene> initiates a hydride transfer from the one of the two methyl groups bound to the nitrogen at the lysine tail, via a N5 on the flavin group. An imine cation is then formed at the end of the lysine tail to compensate for the loss of hydride. In the next step the imine is hydrolyzed and transitions to an Hemiaminal. This then breaks down easily to formaldehyde and the product lysine.
+The methylation of lysine via LSD1 occurs through a 2 electron process. Shown in Figure 3 the first step involves the <scene name='81/811710/Fad_highlight/1'>Flavin Adenine Dinucleotide cofactor</scene> initiating a hydride transfer from the one of the two methyl groups bound to the nitrogen at the lysine tail, via a N5 on the flavin group. An imine cation is then formed at the end of the lysine tail to compensate for the loss of hydride. In the next step the imine is hydrolyzed and transitions to an Hemiaminal. This then breaks down easily to formaldehyde and the product lysine.
-[[Image:LSD1 Mech.jpg|400px|right|thumb|Mechanism]]
+[[Image:LSD1 Mech.jpg|400px|right|thumb|Figure 3]]
 ===Hydrophobic Pocket===

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Revision as of 16:46, 9 April 2019

LSD Demethylase

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