Backbone and sidechain 1H, 13C and 15N resonance assignments of the Bright/ARID domain from the human JARID1C (SMCX) protein

Koehler, Christian; Bishop, Shurene; Dowler, Elizabeth F.; Schmieder, Peter; Diehl, Anne; Oschkinat, Hartmut; Ball, Linda

doi:10.1007/s12104-007-9071-7

Cited by 15 publications

(11 citation statements)

References 7 publications

(7 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As mentioned above, KDM5C is multi‐domain protein consisting of well‐defined domains as JmjN, ARID, PHD, JmjC and ZF domains. For most of them, JmjN, ARID, JmjC and ZF domains, there is experimental 3D structure available (Protein Data Bank (PDB) ID:2JRZ and 5FWJ) . However, the 3D structure of PHD1 domain is not available and must be modeled.…”

Section: Resultsmentioning

confidence: 99%

“…Little experimental data is available about the 3D structure of the entire protein, individual domains and the interactions with its partners. The first experimental structure of one of the KDM5C domains is the solution structure of ARID domain, released in 2007 . In the past, we used it to generate a 3D model of the ARID‐DNA complex .…”

Section: Introductionmentioning

confidence: 99%

“…The first experimental structure of one of the KDM5C domains is the solution structure of ARID domain, released in 2007. 11 In the past, we used it to generate a 3D model of the ARID-DNA complex. 9 Very recently, the 3D structure of part of the human KDM5C protein (JmjN, JmjC and ZF domains) was released.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Cofactors-loaded quaternary structure of lysine-specific demethylase 5C (KDM5C) protein: Computational model

Peng

Alexov

2016

Proteins

View full text Add to dashboard Cite

The KDM5C gene (also known as JARID1C and SMCX) is located on the X chromosome and encodes a ubiquitously expressed 1,560-aa protein, which plays an important role in lysine methylation (specifically reverses tri- and di-methylation of Lys4 of histone H3). Currently, thirteen missense mutations in KDM5C have been linked to X-linked mental retardation. However, the molecular mechanism of disease is currently unknown due to the experimental difficulties in expressing such large protein and the lack of experimental 3D structure. In this work, we utilize homology modeling, docking, and experimental data to predict 3D structures of KDM5C domains and their mutual arrangement. The resulting quaternary structure includes KDM5C JmjN, ARID, PHD1, JmjC, ZF domains, substrate histone peptide, enzymatic cofactors and DNA. The predicted quaternary structure was investigated with molecular dynamic simulation for its stability, and further analysis was carried out to identify features measured experimentally. The predicted structure of KDM5C was used to investigate the effects of disease-causing mutations and it was shown that the mutations alter domain stability and inter-domain interactions. The structural model reported in this work could prompt experimental investigations of KDM5C domain-domain interaction and exploration of undiscovered functionalities.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Cofactors-loaded quaternary structure of lysine-specific demethylase 5C (KDM5C) protein: Computational model

Peng

Alexov

2016

Proteins

View full text Add to dashboard Cite

show abstract

“…The ARID domain contains 90 amino acids and its sequence is mapped onto the KDM5C protein sequence from position 79 to 169. There is an NMR structure of the KDM5C ARID domain (PDB ID: 2JRZ) [ 40 ] in the Protein Data Bank (PDB) [ 22 ], which was used for modeling the ARID domain stability. The modeling of the effect of mutations on ARID-DNA interactions requires the 3D structure of ARID-DNA complex, which is not available in the PDB and was generated in silico .…”

Section: Methods and Experimental Sectionmentioning

confidence: 99%

Mutations in the KDM5C ARID Domain and Their Plausible Association with Syndromic Claes-Jensen-Type Disease

Peng

Suryadi

Yang

et al. 2015

IJMS

View full text Add to dashboard Cite

Mutations in KDM5C gene are linked to X-linked mental retardation, the syndromic Claes-Jensen-type disease. This study focuses on non-synonymous mutations in the KDM5C ARID domain and evaluates the effects of two disease-associated missense mutations (A77T and D87G) and three not-yet-classified missense mutations (R108W, N142S, and R179H). We predict the ARID domain’s folding and binding free energy changes due to mutations, and also study the effects of mutations on protein dynamics. Our computational results indicate that A77T and D87G mutants have minimal effect on the KDM5C ARID domain stability and DNA binding. In parallel, the change in the free energy unfolding caused by the mutants A77T and D87G were experimentally measured by urea-induced unfolding experiments and were shown to be similar to the in silico predictions. The evolutionary conservation analysis shows that the disease-associated mutations are located in a highly-conserved part of the ARID structure (N-terminal domain), indicating their importance for the KDM5C function. N-terminal residues’ high conservation suggests that either the ARID domain utilizes the N-terminal to interact with other KDM5C domains or the N-terminal is involved in some yet unknown function. The analysis indicates that, among the non-classified mutations, R108W is possibly a disease-associated mutation, while N142S and R179H are probably harmless.

show abstract

“…[206] presented the crystal structures JMJD2A in complex with the trimethyl form of H3-K4 and JMJD2A in complex with the trimethyl form of H4-K20, showing that the two histones adopt radically different binding modes. Other JmjC domain-containing demethylase structures include the DNA binding domain of the H3-K4 demethylase RBP2 [207], the DNA binding domain of JARID1C [208], and solution structure of JARID1A [209]. …”

Section: Application Domainsmentioning

confidence: 99%

Computational Methods for De novo Protein Design and its Applications to the Human Immunodeficiency Virus 1, Purine Nucleoside Phosphorylase, Ubiquitin Specific Protease 7, and Histone Demethylases

Bellows¹,

Floudas²

2010

CDT

View full text Add to dashboard Cite

This paper provides an overview of computational de novo protein design methods, highlighting recent advances and successes. Four protein systems are described that are important targets for drug design: human immunodeficiency virus 1, purine nucleoside phosphorylase, ubiquitin specific protease 7, and histone demethylases. Target areas for drug design for each protein are described, along with known inhibitors, focusing on peptidic inhibitors, but also describing some smallmolecule inhibitors. Computational design methods that have been employed in elucidating these inhibitors for each protein are outlined, along with steps that can be taken in order to apply computational protein design to a system that has mainly used experimental methods to date. KeywordsComputational protein design; human immunodeficiency virus 1; purine nucleoside phosphorylase; ubiquitin specific protease 7; histone demethylases

show abstract

Backbone and sidechain 1H, 13C and 15N resonance assignments of the Bright/ARID domain from the human JARID1C (SMCX) protein

Cited by 15 publications

References 7 publications

Cofactors-loaded quaternary structure of lysine-specific demethylase 5C (KDM5C) protein: Computational model

Cofactors-loaded quaternary structure of lysine-specific demethylase 5C (KDM5C) protein: Computational model

Mutations in the KDM5C ARID Domain and Their Plausible Association with Syndromic Claes-Jensen-Type Disease

Computational Methods for De novo Protein Design and its Applications to the Human Immunodeficiency Virus 1, Purine Nucleoside Phosphorylase, Ubiquitin Specific Protease 7, and Histone Demethylases

Contact Info

Product

Resources

About