Structural genomics of histone tail recognition

Wang, Minghua; Mok, Man Wai; Harper, Hong; Lee, Wen‐Hwa; Min, Jinrong; Knapp, Stefan; Oppermann, U.; Schapira, Matthieu

doi:10.1093/bioinformatics/btq491

Cited by 10 publications

(7 citation statements)

References 23 publications

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“…Necessary epigenomic reprogramming of histone modification at different stages of cell development is affected by the activation of histone and lysine-specific demethylase enzymes (Table 18). Determinants for recognition of the histone code are being revealed by a growing body of experimental data providing valuable information on the molecular tractability of binding sites involved in epigenetic signalling [501], which will enhance further insight to epigenetic function.…”

Section: Discussionmentioning

confidence: 99%

KEGG orthology-based annotation of the predicted proteome of Acropora digitifera: ZoophyteBase - an open access and searchable database of a coral genome

et al. 2013

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BackgroundContemporary coral reef research has firmly established that a genomic approach is urgently needed to better understand the effects of anthropogenic environmental stress and global climate change on coral holobiont interactions. Here we present KEGG orthology-based annotation of the complete genome sequence of the scleractinian coral Acropora digitifera and provide the first comprehensive view of the genome of a reef-building coral by applying advanced bioinformatics.DescriptionSequences from the KEGG database of protein function were used to construct hidden Markov models. These models were used to search the predicted proteome of A. digitifera to establish complete genomic annotation. The annotated dataset is published in ZoophyteBase, an open access format with different options for searching the data. A particularly useful feature is the ability to use a Google-like search engine that links query words to protein attributes. We present features of the annotation that underpin the molecular structure of key processes of coral physiology that include (1) regulatory proteins of symbiosis, (2) planula and early developmental proteins, (3) neural messengers, receptors and sensory proteins, (4) calcification and Ca2+-signalling proteins, (5) plant-derived proteins, (6) proteins of nitrogen metabolism, (7) DNA repair proteins, (8) stress response proteins, (9) antioxidant and redox-protective proteins, (10) proteins of cellular apoptosis, (11) microbial symbioses and pathogenicity proteins, (12) proteins of viral pathogenicity, (13) toxins and venom, (14) proteins of the chemical defensome and (15) coral epigenetics.ConclusionsWe advocate that providing annotation in an open-access searchable database available to the public domain will give an unprecedented foundation to interrogate the fundamental molecular structure and interactions of coral symbiosis and allow critical questions to be addressed at the genomic level based on combined aspects of evolutionary, developmental, metabolic, and environmental perspectives.

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Section: Discussionmentioning

confidence: 99%

KEGG orthology-based annotation of the predicted proteome of Acropora digitifera: ZoophyteBase - an open access and searchable database of a coral genome

et al. 2013

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“…Surprisingly, in all available structures, an arginine side-chain located one to four residues upstream or downstream the substrate lysine is the next most important contributor to interaction, and makes extensive contacts with a well-defined cleft of the I-SET domain (Fig. 4 ) [ 14 , 18 , 19 , 21 , 24 ]. Interestingly, the shape, structural environment, and position of this cleft relative to the lysine binding channel varies from one enzyme to the other, suggesting that it could be exploited to design selective inhibitors.…”

Section: Substrate Recognitionmentioning

confidence: 99%

Structural Chemistry of Human SET Domain Protein Methyltransferases

Schapira¹

2011

Curr Chem Genomics

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103

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There are about fifty SET domain protein methyltransferases (PMTs) in the human genome, that transfer a methyl group from S-adenosyl-L-methionine (SAM) to substrate lysines on histone tails or other peptides. A number of structures in complex with cofactor, substrate, or inhibitors revealed the mechanisms of substrate recognition, methylation state specificity, and chemical inhibition. Based on these structures, we review the structural chemistry of SET domain PMTs, and propose general concepts towards the development of selective inhibitors.

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“…A large body of structural data is available on these binding modules, with over 50 such domains solved in complex with histone peptides [22,23]. In this work, we analyze these structures to derive a druggability landscape across the major classes of methyl-lysine readers, and understand the structural features that drive druggability.…”

Section: Introductionmentioning

confidence: 99%

Druggability of methyl-lysine binding sites

Santiago

Nguyen

Schapira

2011

J Comput Aided Mol Des

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Structural modules that specifically recognize--or read--methylated or acetylated lysine residues on histone peptides are important components of chromatin-mediated signaling and epigenetic regulation of gene expression. Deregulation of epigenetic mechanisms is associated with disease conditions, and antagonists of acetyl-lysine binding bromodomains are efficacious in animal models of cancer and inflammation, but little is known regarding the druggability of methyl-lysine binding modules. We conducted a systematic structural analysis of readers of methyl marks and derived a predictive druggability landscape of methyl-lysine binding modules. We show that these target classes are generally less druggable than bromodomains, but that some proteins stand as notable exceptions.

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Structural genomics of histone tail recognition

Cited by 10 publications

References 23 publications

KEGG orthology-based annotation of the predicted proteome of Acropora digitifera: ZoophyteBase - an open access and searchable database of a coral genome

KEGG orthology-based annotation of the predicted proteome of Acropora digitifera: ZoophyteBase - an open access and searchable database of a coral genome

Structural Chemistry of Human SET Domain Protein Methyltransferases

Druggability of methyl-lysine binding sites

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