User:Elisha Lacey/Sandbox 1

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Bromodomain testis specific

The human genome has 56 bromodomains across 42 proteins. Bromodomains are found in mammals. Bromodomain testis specific (BRDT) also known as known as CT9 and RING3-like protein and belongs to the bromodomain extra terminal (BET) family. BRDT is expressed in pachytene and diplotene spermatocytes and round spermatids.

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.

1 Function
2 BRDT and fertility
3 Relevance
4 Analysis of Structure
5 Analysis of related Sequences
6 Evolution of BRDT

Function

Bromodomain testis specific is a monomer that is only fully functional as a dimer. BRDT is a transcriptional regulator for gene expression during spermatogenesis.

BRDT and fertility

Loss of one of the bromodomains leads to decrease spermatogenesis and defective sperm. If both bromodomains are knocked out it leads to loss of fertility.

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.

Analysis of Structure

The functional unit for BRDT is two bromodomain motifs, each monomer is composed of 4 anti-parallel alpha helixes.

Analysis of related Sequences

Evolution of BRDT

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 by Group, and another to make of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

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.

↑ 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
↑ 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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Bromodomain testis specific

Contents

Function

BRDT and fertility

Relevance

Analysis of Structure

Analysis of related Sequences

Evolution of BRDT

References

Proteopedia Page Contributors and Editors (what is this?)

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