scholarly journals Structural analysis of human dual-specificity phosphatase 22 complexed with a phosphotyrosine-like substrate

2015 ◽  
Vol 71 (2) ◽  
pp. 199-205 ◽  
Author(s):  
George T. Lountos ◽  
Scott Cherry ◽  
Joseph E. Tropea ◽  
David S. Waugh
Keyword(s):  
Crystal Structure ◽  
Structural Analysis ◽  
Phosphatase Activity ◽  
Small Molecule ◽  
Molecular Basis ◽  
Protein Tyrosine Phosphatases ◽  
Simple Method ◽  
Dual Specificity Phosphatase ◽  
Dual Specificity ◽  
Nitrophenyl Phosphate

4-Nitrophenyl phosphate (p-nitrophenyl phosphate, pNPP) is widely used as a small molecule phosphotyrosine-like substrate in activity assays for protein tyrosine phosphatases. It is a colorless substrate that upon hydrolysis is converted to a yellow 4-nitrophenolate ion that can be monitored by absorbance at 405 nm. Therefore, the pNPP assay has been widely adopted as a quick and simple method to assess phosphatase activity and is also commonly used in assays to screen for inhibitors. Here, the first crystal structure is presented of a dual-specificity phosphatase, human dual-specificity phosphatase 22 (DUSP22), in complex with pNPP. The structure illuminates the molecular basis for substrate binding and may also facilitate the structure-assisted development of DUSP22 inhibitors.

Identification of new Cdc25 dual specificity phosphatase inhibitors in a targeted small molecule array

2000 ◽  
Vol 8 (6) ◽  
pp. 1451-1466 ◽  
Author(s):  
Alexander P Ducruet ◽  
Robert L Rice ◽  
Kenji Tamura ◽  
Fumiaki Yokokawa ◽  
Shiho Yokokawa ◽  
...  
Keyword(s):  
Small Molecule ◽  
Phosphatase Inhibitors ◽  
Dual Specificity Phosphatase ◽  
Dual Specificity

A Targeted Library of Small-Molecule, Tyrosine, and Dual-Specificity Phosphatase Inhibitors Derived from a Rational Core Design and Random Side Chain Variation†

Biochemistry ◽  
1997 ◽  
Vol 36 (50) ◽  
pp. 15965-15974 ◽  
Author(s):  
Robert L. Rice ◽  
James M. Rusnak ◽  
Fumiaki Yokokawa ◽  
Shiho Yokokawa ◽  
Donald J. Messner ◽  
...  
Keyword(s):  
Small Molecule ◽  
Side Chain ◽  
Phosphatase Inhibitors ◽  
Dual Specificity Phosphatase ◽  
Dual Specificity ◽  
Targeted Library

Crystal structure of human dual specificity phosphatase, JNK stimulatory phosphatase-1, at 1.5 Å resolution

2006 ◽  
Vol 66 (2) ◽  
pp. 272-278 ◽  
Author(s):  
Takehiro Yokota ◽  
Yukinori Nara ◽  
Akiko Kashima ◽  
Keiko Matsubara ◽  
Satoru Misawa ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Dual Specificity Phosphatase ◽  
Dual Specificity

scholarly journals Laforin, a Dual Specificity Phosphatase Involved in Lafora Disease, Is Present Mainly as Monomeric Form with Full Phosphatase Activity

PLoS ONE ◽  
2011 ◽  
Vol 6 (8) ◽  
pp. e24040 ◽  
Author(s):  
Vikas V. Dukhande ◽  
Devin M. Rogers ◽  
Carlos Romá-Mateo ◽  
Jordi Donderis ◽  
Alberto Marina ◽  
...  
Keyword(s):  
Phosphatase Activity ◽  
Monomeric Form ◽  
Lafora Disease ◽  
Dual Specificity Phosphatase ◽  
Dual Specificity

scholarly journals Crystal structure of the human dual specificity phosphatase 1 catalytic domain

2017 ◽  
Vol 27 (2) ◽  
pp. 561-567 ◽  
Author(s):  
Rajesh Gumpena ◽  
George T. Lountos ◽  
Sreejith Raran-Kurussi ◽  
Joseph E. Tropea ◽  
Scott Cherry ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Catalytic Domain ◽  
Dual Specificity Phosphatase ◽  
Dual Specificity

scholarly journals Crystal structure of chromo barrel domain of RBBP1

2018 ◽  
Author(s):  
Ming Lei ◽  
Yue Feng ◽  
Mengqi Zhou ◽  
Yuan Yang ◽  
Peter Loppnau ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Structural Analysis ◽  
Dna Binding ◽  
Surface Charge ◽  
Gene Transcription ◽  
Molecular Basis ◽  
Binding Ability ◽  
Histone Binding ◽  
Multidomain Protein ◽  
Binding Surface

AbstractRBBP1 is a retinoblastoma protein (pRb) binding protein acting as a repressor of gene transcription. RBBP1 is a multidomain protein including a chromo barrel domain, and its chromo barrel domain has been reported to recognize histone H4K20me3 weakly, and this binding is enhanced by the simultaneous binding of DNA. However, the molecular basis of this DNA-mediated histone binding by the chromo barrel domain of RBBP1 is unclear. Here we attempted to co-crystallize the chromo barrel domain of RBBP1 with either a histone H4K20me3 peptide alone or with both a histone H4K20me3 peptide and DNA, but only solved the peptide/DNA unbound crystal structure. Our structural analysis indicates that RBBP1 could interact with histone H4K20me3 similar to other histone binding chromo barrel domains, and the surface charge representation analysis of the chromo barrel domain of RBBP1 suggests that the chromo barrel domain of RBBP1 does not have a typical DNA binding surface, indicating that it might not bind to DNA. Consistently, our ITC assays also showed that DNA does not significantly enhance the histone binding ability of the chromo barrel domain of RBBP1.

scholarly journals Structures of TorsinA and its disease-mutant complexed with an activator reveal the molecular basis for primary dystonia

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
F Esra Demircioglu ◽  
Brian A Sosa ◽  
Jessica Ingram ◽  
Hidde L Ploegh ◽  
Thomas U Schwartz
Keyword(s):  
Crystal Structure ◽  
Endoplasmic Reticulum ◽  
Small Molecule ◽  
Early Onset ◽  
Neuromuscular Disease ◽  
Molecular Basis ◽  
Common Cause ◽  
Aaa Atpase ◽  
Primary Dystonia ◽  
Diseased State

The most common cause of early onset primary dystonia, a neuromuscular disease, is a glutamate deletion (ΔE) at position 302/303 of TorsinA, a AAA+ ATPase that resides in the endoplasmic reticulum. While the function of TorsinA remains elusive, the ΔE mutation is known to diminish binding of two TorsinA ATPase activators: lamina-associated protein 1 (LAP1) and its paralog, luminal domain like LAP1 (LULL1). Using a nanobody as a crystallization chaperone, we obtained a 1.4 Å crystal structure of human TorsinA in complex with LULL1. This nanobody likewise stabilized the weakened TorsinAΔE-LULL1 interaction, which enabled us to solve its structure at 1.4 Å also. A comparison of these structures shows, in atomic detail, the subtle differences in activator interactions that separate the healthy from the diseased state. This information may provide a structural platform for drug development, as a small molecule that rescues TorsinAΔE could serve as a cure for primary dystonia.

High-resolution crystal structure of the catalytic domain of human dual-specificity phosphatase 26

2013 ◽  
Vol 69 (6) ◽  
pp. 1160-1170 ◽  
Author(s):  
Eun-Young Won ◽  
Yong Xie ◽  
Chie Takemoto ◽  
Lirong Chen ◽  
Zhi-Jie Liu ◽  
...  
Keyword(s):  
Crystal Structure ◽  
High Resolution ◽  
Catalytic Domain ◽  
Dual Specificity Phosphatase ◽  
Dual Specificity

scholarly journals A novel cinnamic acid derivative that inhibits Cdc25 dual-specificity phosphatase activity

2005 ◽  
Vol 96 (9) ◽  
pp. 614-619 ◽  
Author(s):  
Yoshimi Aoyagi ◽  
Norio Masuko ◽  
Shuichi Ohkubo ◽  
Makoto Kitade ◽  
Kentaro Nagai ◽  
...  
Keyword(s):  
Phosphatase Activity ◽  
Acid Derivative ◽  
Cinnamic Acid ◽  
Cinnamic Acid Derivative ◽  
Dual Specificity Phosphatase ◽  
Dual Specificity
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