Characterization of the active site and a unique uncompetitive inhibitor of the PPM1-type protein phosphatase PPM1D.


:Protein phosphatase magnesium-dependent 1, delta (PPM1D) is a member of the PPM1 (formerly PP2C) protein phosphatase family, and is induced in response to DNA damage. The overexpression of PPM1D is thought to exert oncogenic effects through the inhibition of tumor suppressor proteins. PPM1D shows high selectivity for the primary sequence in its substrates when compared with other phosphatases, but the mechanisms underlying substrate recognition by this enzyme is not clearly known. In our present study we wished to identify the active center and further elucidate the substrate preference of PPM1D, and to this end performed sequence alignments among the human PPM1 type phosphatases. The results of this analysis clearly showed that the putative active site residues of PPM1D are highly conserved among the PPM1 family members. Phosphatase analyses using PPM1D mutants further identified the metal-chelating residues and a phosphate binding residue. In kinetic analyses using a series of phosphorylated p53 peptide analogs, the introduction of acidic residues into the region flanking the sites of dephosphorylation enhanced their affinity with PPM1D. Homology modeling of PPM1D also revealed that PPM1D contains two characteristic loops, a Pro-residue rich loop on the opposite side of the active site and a basic-residue rich loop in the vicinity of the active site in the catalytic domain. Interestingly, nonhydrolyzable AP4-3E peptides derived from the acidic p53 peptide analogs very effectively blocked PPM1D activity in an uncompetitive manner, suggesting that AP4-3E peptides may be useful lead compounds in the development of novel inhibitors of PPM1D.


Protein Pept Lett


Chuman Y,Yagi H,Fukuda T,Nomura T,Matsukizono M,Shimohigashi Y,Sakaguchi K




Has Abstract


2008-01-01 00:00:00












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    abstract::Porins are integral membrane proteins found in the outer membrane of bacteria, mitochondria and chloroplasts. Herein, we have reviewed sequence and structural understanding about bacterial porins. The first porin structure from Rhodobacter capsulatus at 1.8 Å resolution in 1991 till the recent structural advancement, ...

    journal_title:Protein and peptide letters

    pub_type: 杂志文章


    authors: Kumar A,Bhandari A,Krishnaswamy S

    更新日期:2015-01-01 00:00:00

  • Complementary peptide epitopes and anti-idiotypic antibodies in autoimmunity.

    abstract::Application of complementary B and T cell epitopes in inducing anti-idiotypic and anti-clonotypic antibodies capable of regulating or suppressing the autoimmune responses in experimental autoimmune myasthenia gravis (EAMG), allergic neuritis (EAN) and allergic encephalomyelitis (EAE) has been the stimulus of many rese...

    journal_title:Protein and peptide letters

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    authors: Sakarellos-Daitsiotis M,Cung MT,Sakarellos C,El Hilali Z,Kosmopoulou A,Voitharou C

    更新日期:2004-08-01 00:00:00

  • Functional and Catalytic Characterization of the Detoxifying Enzyme Haloalkane Dehalogenase from Rhizobium leguminosarum.

    abstract:BACKGROUND:Haloalkane dehalogenases (EC, HLDs) are α/β-hydrolases which catalyze the irreversible cleavage of carbon-halogen bonds of haloalkanes, producing an alcohol, a halide and a hydrogen ion. Haloalkanes are acutely toxic to animals and humans and their toxic effects are mainly observed in the liver, kidn...

    journal_title:Protein and peptide letters

    pub_type: 杂志文章


    authors: Georgakis N,Chronopoulou E,Gad MA,Skliros D,Efrose R,Flemetakis E,Labrou NE

    更新日期:2017-01-01 00:00:00

  • Identification of heterotrimeric G protein α and β subunits in rice.

    abstract::Like those in mammals, heterotrimeric G protein complexes have been implicated in signal transduction pathways in plants; however, the subunits themselves have not been isolated. In this study, the rice heterotrimeric G protein subunits α (Gα) and β (Gβ) were purified by affinity chromatography using anti-Gα and -Gβ a...

    journal_title:Protein and peptide letters

    pub_type: 杂志文章


    authors: Abe Y,Matsusita K,Komatsu S,Iwasaki Y

    更新日期:2012-03-01 00:00:00

  • An RGD-Modified Endostatin Peptide Expressed at E. coli Shows Anti-Tumor Activity In vivo.

    abstract::Tumor vasculatures express high levels of α(V)β(3)/α(V)β(5) and α(5)β(1) integrins. Peptide containing the RGD (Arg-Gly-Asp) sequence, which is present in ligands of integrins, is effective in targeting therapeutic reagents to tumor vascular endothelium. In this study, we investigated whether the biological activity o...

    journal_title:Protein and peptide letters

    pub_type: 杂志文章


    authors: Zhang HT,Li HC,Li ZW,Guo CH,Chen YJ

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    journal_title:Protein and peptide letters

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    authors: Silva HC,Bari AU,Pereira-Jénior FN,Simões RC,Barroso-Neto IL,Nobre CB,Pereira MG,Nascimento KS,Rocha BA,Delatorre P,Nagano CS,Assreuy AM,Cavada BS

    更新日期:2011-04-01 00:00:00

  • Effect of Temperature and pH on the Secondary Structure and Denaturation Process of Jumbo Squid Hepatopancreas Cathepsin D.

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    journal_title:Protein and peptide letters

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    authors: Nose T,Shimohigashi Y

    更新日期:2008-01-01 00:00:00

  • Kinetics of inactivation of phytase (phy A) during modification of histidine residue by IAA and DEP.

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  • Logical Analysis of Regulation of Interleukin-12 Expression Pathway Regulation During HCV Infection.

    abstract::Hepatitis C virus (HCV) triggers coordinated innate and adaptive response in host cell. HCV genome and proteins of the replicating virus are recognized as non-self-antigens by host cell to activate Toll Like Receptors (TLRs). Activated TLRs ultimately express cytokines, which can clear virus either by activating inter...

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    authors: Farooqi ZU,Tareen SH,Ahmed J,Zaidi NU

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  • A Proteomics Approach to Discover Drought Tolerance Proteins in Wheat Pollen Grain at Meiosis Stage.

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    authors: Fotovat R,Alikhani M,Valizadeh M,Mirzaei M,Salekdeh GH

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    authors: Wu G,Zhang ZL,Fu CJ,Lv FL,Tian FF

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    authors: Fulda S,Linseisen J,Wolfram G,Himmerich S,Gedrich K,Pollmächer T,Himmerich H

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    journal_title:Protein and peptide letters

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    authors: Bhat RK,Berger S

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    authors: Raüber C,Berger S

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    authors: Chen Z,Kanapathipillai M

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    abstract::The stability of Merrifield linker in Fmoc deprotection process was quantitatively investigated by establishing working curve of two major decomposition components from two resin bound dipeptide models. By sampling reaction solution and analyzing with RP-HPLC, decomposition rate was determined. The results indicated t...

    journal_title:Protein and peptide letters

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    abstract::The identification of interfaces in protein complexes is effective for the elucidation of protein function and helps us to understand their roles in biological processes. With the exponentially growing amount of protein sequence data, an exploration of new methods that predict protein interaction sites based solely on...

    journal_title:Protein and peptide letters

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    authors: Huang J,Deng R,Wang J,Wu H,Xiong Y,Wang X

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  • Detection of antibodies against synthetic peptides mimicking ureases fragments in sera of rheumatoid arthritis patients.

    abstract::Rheumatoid arthritis (RA) is a chronic disease with an autoimmunological background. RA is mostly characterized by systemic inflammation and injuries of synovial joints. There is a hypothesis that bacterial infections may be connected with development of the disease. It has been suggested that molecular mimicry betwee...

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    pub_type: 杂志文章


    authors: Konieczna I,Kwinkowski M,Kolesińska B,Kamiński Z,Zarnowiec P,Kaca W

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  • Cloning and expression of a new rat procarboxypeptidase B gene in Escherichia coli and purification of recombination carboxypeptidase B.

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    journal_title:Protein and peptide letters

    pub_type: 杂志文章


    authors: Su-Xia L,Yu-Jian Z,Li-Ping T,Qin-Sheng Y,Yi G

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    abstract::The P2 protein (equivalent of L7/L12 in prokaryotes), a member of the ribosomal stalk in eukaryotes, is highly conserved, particularly its C-terminal domain. In order to understand the sequence-structure-function relationships in eukaryotic C-terminal stretches, about which nothing is known at the moment, we have inve...

    journal_title:Protein and peptide letters

    pub_type: 杂志文章


    authors: Mishra P,Rajagopal S,Sharma S,Hosur RV

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  • Isoform characterisation, heterologous expression and functional analysis of two lectins from Vatairea macrocarpa.

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    journal_title:Protein and peptide letters

    pub_type: 杂志文章


    authors: Alves Filho JG,do Nascimento AS,Gondim AC,Pereira RH,da Cunha RM,Nagano CS,Teixeira EH,Nascimento KS,Cavada BS

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    journal_title:Protein and peptide letters

    pub_type: 杂志文章


    authors: Kurt F

    更新日期:2020-06-25 00:00:00

  • Alternative nucleophilic residues in intein catalysis of protein splicing.

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    journal_title:Protein and peptide letters

    pub_type: 杂志文章


    authors: Qi X,Wang J,Meng Q,Liu XQ

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    journal_title:Protein and peptide letters

    pub_type: 杂志文章


    authors: Joshi RR,Manda C

    更新日期:2007-01-01 00:00:00

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    journal_title:Protein and peptide letters

    pub_type: 杂志文章


    authors: dos Santos LD,Dias NB,Roberto J,Pinto AS,Palma MS

    更新日期:2009-01-01 00:00:00