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'''Unreleased structure'''


The entry 6g0o is ON HOLD
==Crystal Structure of the first bromodomain of human BRD4 in complex with an acetylated ATRX peptide (K1030ac/K1033ac)==
 
<StructureSection load='6g0o' size='340' side='right' caption='[[6g0o]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
Authors: Filippakopoulos, P., Picaud, S., Newman, J., Sorrell, F., von Delft, F., Arrowsmith, C.H., Edwards, A.M., Bountra, C.
== Structural highlights ==
 
<table><tr><td colspan='2'>[[6g0o]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6G0O OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6G0O FirstGlance]. <br>
Description: Crystal Structure of the first bromodomain of human BRD4 in complex with an acetylated ATRX peptide (K1030ac/K1033ac)
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
[[Category: Unreleased Structures]]
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ALY:N(6)-ACETYLLYSINE'>ALY</scene></td></tr>
[[Category: Arrowsmith, C.H]]
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BRD4, HUNK1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
[[Category: Von Delft, F]]
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA_helicase DNA helicase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.4.12 3.6.4.12] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6g0o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6g0o OCA], [http://pdbe.org/6g0o PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6g0o RCSB], [http://www.ebi.ac.uk/pdbsum/6g0o PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6g0o ProSAT]</span></td></tr>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN]] Note=A chromosomal aberration involving BRD4 is found in a rare, aggressive, and lethal carcinoma arising in midline organs of young people. Translocation t(15;19)(q14;p13) with NUT which produces a BRD4-NUT fusion protein.<ref>PMID:12543779</ref> <ref>PMID:11733348</ref>  [[http://www.uniprot.org/uniprot/ATRX_HUMAN ATRX_HUMAN]] Defects in ATRX are the cause of alpha-thalassemia mental retardation syndrome X-linked (ATRX) [MIM:[http://omim.org/entry/301040 301040]]. ATR-X is an X-linked disorder comprising severe psychomotor retardation, facial dysmorphism, urogenital abnormalities, and alpha-thalassemia. An essential phenotypic trait are hemoglobin H erythrocyte inclusions.<ref>PMID:8968741</ref> <ref>PMID:7697714</ref> <ref>PMID:9043863</ref> <ref>PMID:9326931</ref> <ref>PMID:10660327</ref> <ref>PMID:10417298</ref> <ref>PMID:10204841</ref> <ref>PMID:10995512</ref> <ref>PMID:12116232</ref> <ref>PMID:16955409</ref>  Defects in ATRX are the cause of mental retardation syndromic X-linked with hypotonic facies syndrome type 1 (MRXSHF1) [MIM:[http://omim.org/entry/309580 309580]]; also called Carpenter-Waziri syndrome (CWS), Juberg-Marsidi syndrome (JMS), Smith-Fineman-Myers syndrome type 1 (SFM1). Clinical features include severe mental retardation, dysmorphic facies, and a highly skewed X-inactivation pattern in carrier women. Other more variable features include hypogonadism, deafness, renal anomalies, and mild skeletal defects.<ref>PMID:10751095</ref> <ref>PMID:8630485</ref> <ref>PMID:10398237</ref> <ref>PMID:11050622</ref> <ref>PMID:16222662</ref> <ref>PMID:15565397</ref>  Defects in ATRX are a cause of alpha-thalassemia myelodysplasia syndrome (ATMDS) [MIM:[http://omim.org/entry/300448 300448]]. In this disorder, alpha-thalassemia occurs as an acquired abnormality in association with a multilineage myelodysplasia.<ref>PMID:12858175</ref> 
== Function ==
[[http://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN]] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity). [[http://www.uniprot.org/uniprot/ATRX_HUMAN ATRX_HUMAN]] Could be a global transcriptional regulator. Modifies gene expression by affecting chromatin. May be involved in brain development and facial morphogenesis.
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: DNA helicase]]
[[Category: Human]]
[[Category: Arrowsmith, C H]]
[[Category: Bountra, C]]
[[Category: Delft, F von]]
[[Category: Edwards, A M]]
[[Category: Filippakopoulos, P]]
[[Category: Newman, J]]
[[Category: Picaud, S]]
[[Category: Picaud, S]]
[[Category: Newman, J]]
[[Category: Filippakopoulos, P]]
[[Category: Edwards, A.M]]
[[Category: Bountra, C]]
[[Category: Sorrell, F]]
[[Category: Sorrell, F]]
[[Category: Bromodomain]]
[[Category: Complex]]
[[Category: Transcription]]

Revision as of 23:30, 2 December 2018

Crystal Structure of the first bromodomain of human BRD4 in complex with an acetylated ATRX peptide (K1030ac/K1033ac)Crystal Structure of the first bromodomain of human BRD4 in complex with an acetylated ATRX peptide (K1030ac/K1033ac)

Structural highlights

6g0o is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
NonStd Res:
Gene:BRD4, HUNK1 (HUMAN)
Activity:DNA helicase, with EC number 3.6.4.12
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[BRD4_HUMAN] Note=A chromosomal aberration involving BRD4 is found in a rare, aggressive, and lethal carcinoma arising in midline organs of young people. Translocation t(15;19)(q14;p13) with NUT which produces a BRD4-NUT fusion protein.[1] [2] [ATRX_HUMAN] Defects in ATRX are the cause of alpha-thalassemia mental retardation syndrome X-linked (ATRX) [MIM:301040]. ATR-X is an X-linked disorder comprising severe psychomotor retardation, facial dysmorphism, urogenital abnormalities, and alpha-thalassemia. An essential phenotypic trait are hemoglobin H erythrocyte inclusions.[3] [4] [5] [6] [7] [8] [9] [10] [11] [12] Defects in ATRX are the cause of mental retardation syndromic X-linked with hypotonic facies syndrome type 1 (MRXSHF1) [MIM:309580]; also called Carpenter-Waziri syndrome (CWS), Juberg-Marsidi syndrome (JMS), Smith-Fineman-Myers syndrome type 1 (SFM1). Clinical features include severe mental retardation, dysmorphic facies, and a highly skewed X-inactivation pattern in carrier women. Other more variable features include hypogonadism, deafness, renal anomalies, and mild skeletal defects.[13] [14] [15] [16] [17] [18] Defects in ATRX are a cause of alpha-thalassemia myelodysplasia syndrome (ATMDS) [MIM:300448]. In this disorder, alpha-thalassemia occurs as an acquired abnormality in association with a multilineage myelodysplasia.[19]

Function

[BRD4_HUMAN] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity). [ATRX_HUMAN] Could be a global transcriptional regulator. Modifies gene expression by affecting chromatin. May be involved in brain development and facial morphogenesis.

References

  1. ↑ French CA, Miyoshi I, Kubonishi I, Grier HE, Perez-Atayde AR, Fletcher JA. BRD4-NUT fusion oncogene: a novel mechanism in aggressive carcinoma. Cancer Res. 2003 Jan 15;63(2):304-7. PMID:12543779
  2. ↑ French CA, Miyoshi I, Aster JC, Kubonishi I, Kroll TG, Dal Cin P, Vargas SO, Perez-Atayde AR, Fletcher JA. BRD4 bromodomain gene rearrangement in aggressive carcinoma with translocation t(15;19). Am J Pathol. 2001 Dec;159(6):1987-92. PMID:11733348 doi:10.1016/S0002-9440(10)63049-0
  3. ↑ Picketts DJ, Higgs DR, Bachoo S, Blake DJ, Quarrell OW, Gibbons RJ. ATRX encodes a novel member of the SNF2 family of proteins: mutations point to a common mechanism underlying the ATR-X syndrome. Hum Mol Genet. 1996 Dec;5(12):1899-907. PMID:8968741
  4. ↑ Gibbons RJ, Picketts DJ, Villard L, Higgs DR. Mutations in a putative global transcriptional regulator cause X-linked mental retardation with alpha-thalassemia (ATR-X syndrome). Cell. 1995 Mar 24;80(6):837-45. PMID:7697714
  5. ↑ Villard L, Lacombe D, Fontes M. A point mutation in the XNP gene, associated with an ATR-X phenotype without alpha-thalassemia. Eur J Hum Genet. 1996;4(6):316-20. PMID:9043863
  6. ↑ Gibbons RJ, Bachoo S, Picketts DJ, Aftimos S, Asenbauer B, Bergoffen J, Berry SA, Dahl N, Fryer A, Keppler K, Kurosawa K, Levin ML, Masuno M, Neri G, Pierpont ME, Slaney SF, Higgs DR. Mutations in transcriptional regulator ATRX establish the functional significance of a PHD-like domain. Nat Genet. 1997 Oct;17(2):146-8. PMID:9326931 doi:10.1038/ng1097-146
  7. ↑ Fichera M, Romano C, Castiglia L, Failla P, Ruberto C, Amata S, Greco D, Cardoso C, Fontes M, Ragusa A. New mutations in XNP/ATR-X gene: a further contribution to genotype/phenotype relationship in ATR/X syndrome. Mutations in brief no. 176. Online. Hum Mutat. 1998;12(3):214. PMID:10660327
  8. ↑ Lossi AM, Millan JM, Villard L, Orellana C, Cardoso C, Prieto F, Fontes M, Martinez F. Mutation of the XNP/ATR-X gene in a family with severe mental retardation, spastic paraplegia and skewed pattern of X inactivation: demonstration that the mutation is involved in the inactivation bias. Am J Hum Genet. 1999 Aug;65(2):558-62. PMID:10417298 doi:10.1086/302499
  9. ↑ Villard L, Bonino MC, Abidi F, Ragusa A, Belougne J, Lossi AM, Seaver L, Bonnefont JP, Romano C, Fichera M, Lacombe D, Hanauer A, Philip N, Schwartz C, Fontes M. Evaluation of a mutation screening strategy for sporadic cases of ATR-X syndrome. J Med Genet. 1999 Mar;36(3):183-6. PMID:10204841
  10. ↑ Wada T, Kubota T, Fukushima Y, Saitoh S. Molecular genetic study of japanese patients with X-linked alpha-thalassemia/mental retardation syndrome (ATR-X). Am J Med Genet. 2000 Sep 18;94(3):242-8. PMID:10995512
  11. ↑ Yntema HG, Poppelaars FA, Derksen E, Oudakker AR, van Roosmalen T, Jacobs A, Obbema H, Brunner HG, Hamel BC, van Bokhoven H. Expanding phenotype of XNP mutations: mild to moderate mental retardation. Am J Med Genet. 2002 Jul 1;110(3):243-7. PMID:12116232 doi:10.1002/ajmg.10446
  12. ↑ Badens C, Martini N, Courrier S, DesPortes V, Touraine R, Levy N, Edery P. ATRX syndrome in a girl with a heterozygous mutation in the ATRX Zn finger domain and a totally skewed X-inactivation pattern. Am J Med Genet A. 2006 Oct 15;140(20):2212-5. PMID:16955409 doi:10.1002/ajmg.a.31400
  13. ↑ Villard L, Fontes M, Ades LC, Gecz J. Identification of a mutation in the XNP/ATR-X gene in a family reported as Smith-Fineman-Myers syndrome. Am J Med Genet. 2000 Mar 6;91(1):83-5. PMID:10751095
  14. ↑ Villard L, Gecz J, Mattei JF, Fontes M, Saugier-Veber P, Munnich A, Lyonnet S. XNP mutation in a large family with Juberg-Marsidi syndrome. Nat Genet. 1996 Apr;12(4):359-60. PMID:8630485 doi:http://dx.doi.org/10.1038/ng0496-359
  15. ↑ Abidi F, Schwartz CE, Carpenter NJ, Villard L, Fontes M, Curtis M. Carpenter-Waziri syndrome results from a mutation in XNP. Am J Med Genet. 1999 Jul 30;85(3):249-51. PMID:10398237
  16. ↑ Stevenson RE, Abidi F, Schwartz CE, Lubs HA, Holmes LB. Holmes-Gang syndrome is allelic with XLMR-hypotonic face syndrome. Am J Med Genet. 2000 Oct 23;94(5):383-5. PMID:11050622
  17. ↑ Leahy RT, Philip RK, Gibbons RJ, Fisher C, Suri M, Reardon W. Asplenia in ATR-X syndrome: a second report. Am J Med Genet A. 2005 Nov 15;139(1):37-9. PMID:16222662 doi:10.1002/ajmg.a.30990
  18. ↑ Wieland I, Sabathil J, Ostendorf A, Rittinger O, Ropke A, Winnepenninckx B, Kooy F, Holinski-Feder E, Wieacker P. A missense mutation in the coiled-coil motif of the HP1-interacting domain of ATR-X in a family with X-linked mental retardation. Neurogenetics. 2005 Feb;6(1):45-7. PMID:15565397 doi:10.1007/s10048-004-0190-3
  19. ↑ Gibbons RJ, Pellagatti A, Garrick D, Wood WG, Malik N, Ayyub H, Langford C, Boultwood J, Wainscoat JS, Higgs DR. Identification of acquired somatic mutations in the gene encoding chromatin-remodeling factor ATRX in the alpha-thalassemia myelodysplasia syndrome (ATMDS). Nat Genet. 2003 Aug;34(4):446-9. PMID:12858175 doi:10.1038/ng1213

6g0o, resolution 1.40Å

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