User:Elisha Lacey/Sandbox 1

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== Relevance ==
== Relevance ==
Male contraception has been eluding scientists for years and is a desired area to prevent unplanned pregnancies. In studies of an anti-cancer drug triazolotheinodiaepine known as JQ1 that inhibits BRD4 in cancer pathogenesis. In experiments in mice it is seen, due to structural similarities, JQ1 blocks the production of sperm in testes. The binding of JQ1 in the acetyl-lysine pocket prevents recognition of acetylated histone H4KAC4. JQ1 in studies is not seen to affect hormone levels, mating behaviors or harmful effects to eventual offspring. Also JQ1 is not seen to cause sterility in mice. The effects of JQ1 on fertility are reversible and dose and time dependent effects on fertility.
Male contraception has been eluding scientists for years and is a desired area to prevent unplanned pregnancies. In studies of an anti-cancer drug triazolotheinodiaepine known as JQ1 that inhibits BRD4 in cancer pathogenesis. In experiments in mice it is seen, due to structural similarities, JQ1 blocks the production of sperm in testes. The binding of JQ1 in the acetyl-lysine pocket prevents recognition of acetylated histone H4KAC4. JQ1 in studies is not seen to affect hormone levels, mating behaviors or harmful effects to eventual offspring. Also JQ1 is not seen to cause sterility in mice. The effects of JQ1 on fertility are reversible and dose and time dependent effects on fertility.
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[[Image:JQ1 strucutre.jpg]]
==Analysis of Structure ==
==Analysis of Structure ==
The functional unit for BRDT is two bromodomain motifs, each monomer is composed of 4 anti-parallel alpha helixes.
The functional unit for BRDT is two bromodomain motifs, each monomer is composed of 4 anti-parallel alpha helixes.
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==Evolution of BRDT==
==Evolution of BRDT==
[[Image:BRDT tree.jpg]]
[[Image:BRDT tree.jpg]]
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Looking at the evolution of BRDT it is easy to see why mice are a choice of animal model for assessing fertility affects due to BRDT.
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 03:12, 10 December 2015

Bromodomain testis specific

PDB ID 1stp

Drag the structure with the mouse to rotate

References

Berkovits B, Wolgemuth D. The first bromodomain of the testis-specific double bromodomain protein Brdt is required for chromocenter organization that is modulated by genetic background. PMC. 2011 Dec 15: 360 (2):358-368.

Barda S, Yogev L, Paz G, et al. BRDT gene sequence in human testicular pathologies and the implication of its single nucleotide polymorphism (rs3088232) on fertility. Andrology. 2014 May 28; 2(4): 641-647.

Zdrojewicz Z, Konieczyn R, Papier P, Szten F.Brdt Bromodomains Inhibitors and Other Modern Means of Male Contraception. ACEM. 2015 Feb 23; 24(4):705-714.

  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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Elisha Lacey

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