A PHP Error was encountered

Severity: Warning

Message: fopen(/var/lib/php/sessions/ci_sessionl1jmej91tf405b4ifb4gql6pui6efl9d): Failed to open stream: No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 177

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: session_start(): Failed to read session data: user (path: /var/lib/php/sessions)

Filename: Session/Session.php

Line Number: 137

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Undefined array key "choices"

Filename: controllers/Detail.php

Line Number: 249

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Trying to access array offset on value of type null

Filename: controllers/Detail.php

Line Number: 249

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Trying to access array offset on value of type null

Filename: controllers/Detail.php

Line Number: 249

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Trying to access array offset on value of type null

Filename: controllers/Detail.php

Line Number: 249

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: 8192

Message: strpos(): Passing null to parameter #1 ($haystack) of type string is deprecated

Filename: models/Detail_model.php

Line Number: 71

Backtrace:

File: /var/www/html/application/models/Detail_model.php
Line: 71
Function: strpos

File: /var/www/html/application/controllers/Detail.php
Line: 252
Function: insertAPISummary

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: 8192

Message: str_replace(): Passing null to parameter #3 ($subject) of type array|string is deprecated

Filename: helpers/my_audit_helper.php

Line Number: 8919

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 8919
Function: str_replace

File: /var/www/html/application/controllers/Detail.php
Line: 255
Function: formatAIDetailSummary

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Undefined array key "choices"

Filename: controllers/Detail.php

Line Number: 256

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 256
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Trying to access array offset on value of type null

Filename: controllers/Detail.php

Line Number: 256

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 256
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Trying to access array offset on value of type null

Filename: controllers/Detail.php

Line Number: 256

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 256
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Undefined array key "usage"

Filename: controllers/Detail.php

Line Number: 257

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 257
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Trying to access array offset on value of type null

Filename: controllers/Detail.php

Line Number: 257

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 257
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Undefined array key "usage"

Filename: controllers/Detail.php

Line Number: 258

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 258
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Trying to access array offset on value of type null

Filename: controllers/Detail.php

Line Number: 258

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 258
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Undefined array key "usage"

Filename: controllers/Detail.php

Line Number: 259

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 259
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Trying to access array offset on value of type null

Filename: controllers/Detail.php

Line Number: 259

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 259
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Undefined array key "usage"

Filename: controllers/Detail.php

Line Number: 260

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 260
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Trying to access array offset on value of type null

Filename: controllers/Detail.php

Line Number: 260

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 260
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Trying to access array offset on value of type null

Filename: controllers/Detail.php

Line Number: 260

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 260
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: file_get_contents(https://...@gmail.com&api_key=61f08fa0b96a73de8c900d749fcb997acc09): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests

Filename: helpers/my_audit_helper.php

Line Number: 143

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 143
Function: file_get_contents

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 209
Function: simplexml_load_file_from_url

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3098
Function: getPubMedXML

File: /var/www/html/application/controllers/Detail.php
Line: 574
Function: pubMedSearch_Global

File: /var/www/html/application/controllers/Detail.php
Line: 488
Function: pubMedGetRelatedKeyword

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Attempt to read property "Count" on bool

Filename: helpers/my_audit_helper.php

Line Number: 3100

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3100
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 574
Function: pubMedSearch_Global

File: /var/www/html/application/controllers/Detail.php
Line: 488
Function: pubMedGetRelatedKeyword

File: /var/www/html/index.php
Line: 316
Function: require_once

Identification of a fragment-like small molecule ligand for the methyl-lysine binding protein, 53BP1. | LitMetric

AI Article Synopsis

Article Abstract

Improving our understanding of the role of chromatin regulators in the initiation, development, and suppression of cancer and other devastating diseases is critical, as they are integral players in regulating DNA integrity and gene expression. Developing small molecule inhibitors for this target class with cellular activity is a crucial step toward elucidating their specific functions. We specifically targeted the DNA damage response protein, 53BP1, which uses its tandem tudor domain to recognize histone H4 dimethylated on lysine 20 (H4K20me2), a modification related to double-strand DNA breaks. Through a cross-screening approach, we identified UNC2170 (1) as a micromolar ligand of 53BP1, which demonstrates at least 17-fold selectivity for 53BP1 as compared to other methyl-lysine (Kme) binding proteins tested. Structural studies revealed that the tert-butyl amine of UNC2170 anchors the compound in the methyl-lysine (Kme) binding pocket of 53BP1, making it competitive with endogenous Kme substrates. X-ray crystallography also demonstrated that UNC2170 binds at the interface of two tudor domains of a 53BP1 dimer. Importantly, this compound functions as a 53BP1 antagonist in cellular lysates and shows cellular activity by suppressing class switch recombination, a process which requires a functional 53BP1 tudor domain. These results demonstrate that UNC2170 is a functionally active, fragment-like ligand for 53BP1.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4402254PMC
http://dx.doi.org/10.1021/cb500956gDOI Listing

Publication Analysis

Top Keywords

53bp1
9
small molecule
8
protein 53bp1
8
cellular activity
8
tudor domain
8
ligand 53bp1
8
methyl-lysine kme
8
kme binding
8
identification fragment-like
4
fragment-like small
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!