User:Jaime.Prilusky/Test/Stats

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
* The PDB structures solved with '''Electron Crystallography''' with the '''best resolution''' are [[5k2e]], [[5k2f]] with 1.0 Å each.
+
==Classification==
-
* The PDB structure solved with '''Electron Microscopy''' with the '''best resolution''' is [[5k12]] with 1.8 Å.
+
'''BRCA Exchange''': Pathogenic, '''ClinVar''': Pathogenic
-
* The PDB structures solved with '''Fiber Diffraction''' with the '''best resolution''' are [[1hgv]], [[1hgz]], [[1hh0]] with 2.4 Å each.
+
 
-
* The PDB structure solved with '''Neutron Diffraction''' with the '''best resolution''' is [[4ar3]] with 1.05 Å.
+
== Commentary==
-
* The PDB structure solved with '''Powder Diffraction''' with the '''best resolution''' is [[1ja2]] with 2.87 Å.
+
This mutation Cys61Gly disrupts zinc ion binding necessary for stability of the RING structure [pmid: 22172724, 16403807]. As a consequence, it abolishes interaction with BARD1 and also with E2 conjugate enzymes and thereby reduces its ubiquitin ligase activity. BRCA1 C61G homozygous mice leads to embryonic lethality due to loss of BRCA1 RING function. Drost et al [pmid: 22172724] showed that residual activity of this C61G mutant BRCA1 protein with a dysfunctional RING domain triggers acquired resistance to PARP inhibitors and platinum drugs. For these tumors DNA repair process is partially intact, although homologous recombination (HR) reporter activity is very low. According to Sweet et al [pmid: 19543972], the odds of pathogenicity of this mutation is 5E+05:1, in favor of being deleterious.
-
* The PDB structures solved with '''Solution Scattering''' with the '''best resolution''' are [[1ntj]], [[1ntl]], [[1r70]] with 30.0 Å each.
+
 
-
* The PDB structures solved with '''X-ray Diffraction''' with the '''best resolution''' are [[3nir]], [[5d8v]] with 0.48 Å each.
+
==Experimental results==
-
* The least popular experiment type is Solution Scattering used on 3 structures ([[1ntj]], [[1ntl]], [[1r70]]) over 135,789 ( 0.00%)
+
Heterozygous mutation facilitates tumor development and homozygous mutation is embryonically lethal in a mouse model where p53 is targeted deleted in the mammary gland and BRCA1 deletion is varied according to the required zygosity <ref>pmid 22172724</ref>. High impact in yeast two-hybrid assay <ref>pmid 16403807</ref>.
-
* The mean PDB resolution for structures solved with Electron Crystallography is 4.92 &plusmn; 4.49 based on 70 structures
+
 
-
* The mean PDB resolution for structures solved with Electron Microscopy is 8.67 &plusmn; 8.09 based on 1,818 structures
+
==Impacted biological activities==
-
* The mean PDB resolution for structures solved with Fiber Diffraction is 3.37 &plusmn; 0.7 based on 37 structures
+
E3 Ubiquitin ligase activity Homologous recombination
-
* The mean PDB resolution for structures solved with Neutron Diffraction is 1.93 &plusmn; 0.36 based on 59 structures
+
==Variant==
-
* The mean PDB resolution for structures solved with Powder Diffraction is 3.07 &plusmn; 0.21 based on 6 structures
+
C61G, chr17:g.41258504:A>C, NP_009225.1:p.(Cys61Gly), rs28897672
-
* The mean PDB resolution for structures solved with Solution Scattering is 30 &plusmn; 0 based on 3 structures
+
==Allele Frequency==
-
* The mean PDB resolution for structures solved with X-ray Diffraction is 2.15 &plusmn; 0.58 based on 121,568 structures
+
2.825e-05 (ExAC minus TCGA)
-
* The most popular experiment type is X-ray Diffraction used on 121,568 structures over 135,789 (89.53%)
+
 
-
* The PDB structure solved with '''Electron Crystallography''' with the '''worst resolution''' is [[2dfs]] with 24 &Aring;.
+
 
-
* The PDB structures solved with '''Electron Microscopy''' with the '''worst resolution''' are [[1m8q]], [[1mvw]], [[1o18]], [[1o19]], [[1o1a]], [[1o1b]], [[1o1c]], [[1o1d]], [[1o1e]], [[1o1f]], [[1o1g]] with 70 &Aring; each.
+
==References==
-
* The PDB structures solved with '''Fiber Diffraction''' with the '''worst resolution''' are [[3hqv]], [[3hr2]] with 5.16 &Aring; each.
+
<references/>
-
* The PDB structure solved with '''Neutron Diffraction''' with the '''worst resolution''' is [[1wqz]] with 3.0 &Aring;.
+
-
* The PDB structure solved with '''Powder Diffraction''' with the '''worst resolution''' is [[1xft]] with 3.35 &Aring;.
+
-
* The PDB structures solved with '''Solution Scattering''' with the '''worst resolution''' are [[1ntj]], [[1ntl]], [[1r70]] with 30.0 &Aring; each.
+
-
* The PDB structure solved with '''X-ray Diffraction''' with the '''worst resolution''' is [[2tma]] with 15.0 &Aring;.
+

Revision as of 10:42, 4 November 2018

Contents

Classification

BRCA Exchange: Pathogenic, ClinVar: Pathogenic

Commentary

This mutation Cys61Gly disrupts zinc ion binding necessary for stability of the RING structure [pmid: 22172724, 16403807]. As a consequence, it abolishes interaction with BARD1 and also with E2 conjugate enzymes and thereby reduces its ubiquitin ligase activity. BRCA1 C61G homozygous mice leads to embryonic lethality due to loss of BRCA1 RING function. Drost et al [pmid: 22172724] showed that residual activity of this C61G mutant BRCA1 protein with a dysfunctional RING domain triggers acquired resistance to PARP inhibitors and platinum drugs. For these tumors DNA repair process is partially intact, although homologous recombination (HR) reporter activity is very low. According to Sweet et al [pmid: 19543972], the odds of pathogenicity of this mutation is 5E+05:1, in favor of being deleterious.

Experimental results

Heterozygous mutation facilitates tumor development and homozygous mutation is embryonically lethal in a mouse model where p53 is targeted deleted in the mammary gland and BRCA1 deletion is varied according to the required zygosity [1]. High impact in yeast two-hybrid assay [2].

Impacted biological activities

E3 Ubiquitin ligase activity Homologous recombination

Variant

C61G, chr17:g.41258504:A>C, NP_009225.1:p.(Cys61Gly), rs28897672

Allele Frequency

2.825e-05 (ExAC minus TCGA)


References

  1. ↑ Drost R, Bouwman P, Rottenberg S, Boon U, Schut E, Klarenbeek S, Klijn C, van der Heijden I, van der Gulden H, Wientjens E, Pieterse M, Catteau A, Green P, Solomon E, Morris JR, Jonkers J. BRCA1 RING function is essential for tumor suppression but dispensable for therapy resistance. Cancer Cell. 2011 Dec 13;20(6):797-809. doi: 10.1016/j.ccr.2011.11.014. PMID:22172724 doi:http://dx.doi.org/10.1016/j.ccr.2011.11.014
  2. ↑ Morris JR, Pangon L, Boutell C, Katagiri T, Keep NH, Solomon E. Genetic analysis of BRCA1 ubiquitin ligase activity and its relationship to breast cancer susceptibility. Hum Mol Genet. 2006 Feb 15;15(4):599-606. doi: 10.1093/hmg/ddi476. Epub 2006 Jan , 10. PMID:16403807 doi:http://dx.doi.org/10.1093/hmg/ddi476

Proteopedia Page Contributors and Editors (what is this?)

Jaime Prilusky, Joel L. Sussman

Retrieved from "http://52.214.119.220/wiki/index.php/User:Jaime.Prilusky/Test/Stats"
Personal tools