Peptidomics of prolyl endopeptidase in the central nervous system.


:Prolyl endopeptidase (Prep) is a member of the prolyl peptidase family and is of interest because of its unique biochemistry and connections to cognitive function. Using an unbiased mass spectrometry (MS)-based peptidomics platform, we identified Prep-regulated peptides in the central nervous system (CNS) of mice by measuring changes in the peptidome as a function of Prep activity. This approach was validated by the identification of known Prep substrates, such as the neuropeptide substance P and thymosin-beta4, the precursor to the bioactive peptide Ac-SDKP. In addition to these known substrates, we also discovered that Prep regulates many additional peptides, including additional bioactive peptides and proline rich peptides (PRPs). Biochemical experiments confirmed that some of these Prep-regulated peptides are indeed substrates of the enzyme. Moreover, these experiments also supported the known preference of Prep for shorter peptides while revealing a previously unknown cleavage site specificity of Prep when processing certain multi-proline-containing peptides, including PRPs. The discovery of Prep-regulated peptides implicates Prep in new biological pathways and provides insights into the biochemistry of this enzyme.






Nolte WM,Tagore DM,Lane WS,Saghatelian A




Has Abstract


2009-12-22 00:00:00












  • Rapid isolation of OmpF porin-LPS complexes suitable for structure-function studies.

    abstract::A gentle and rapid isolation procedure is described yielding fractions containing better than 95% pure OmpF porin of Escherichia coli BE with different amounts of bound lipopolysaccharide (LPS). The procedure employs continuous free-flow electrophoresis (FFE) in the presence of detergent above its critical micelle con...


    pub_type: 杂志文章


    authors: Holzenburg A,Engel A,Kessler R,Manz HJ,Lustig A,Aebi U

    更新日期:1989-05-16 00:00:00

  • Mapping the interfacial binding surface of human secretory group IIa phospholipase A2.

    abstract::Human secretory group IIa phospholipase A2 (hIIa-PLA2) contains a large number of prominent cationic patches on its molecular surface and has exceptionally high affinity for anionic surfaces, including anionic membranes. To identify the cationic amino acid residues that support binding of hIIa-PLA2 to anionic membrane...


    pub_type: 杂志文章


    authors: Snitko Y,Koduri RS,Han SK,Othman R,Baker SF,Molini BJ,Wilton DC,Gelb MH,Cho W

    更新日期:1997-11-25 00:00:00

  • Kinetics and processivity of ATP hydrolysis and DNA unwinding by the RecBC enzyme from Escherichia coli.

    abstract::The RecB and RecC subunits of the RecBCD enzyme from Escherichia coli were purified from cells containing plasmids overproducing these proteins [Boehmer, P.E., & Emmerson, P.T. (1991) Gene 102, 1-6]. RecB hydrolyzes ATP in the presence of either single- or double-stranded DNA. RecC stimulates ATP hydrolysis by RecB, p...


    pub_type: 杂志文章


    authors: Korangy F,Julin DA

    更新日期:1993-05-11 00:00:00

  • Bis(pyrrolecarboxamide) linked to intercalating chromophore oxazolopyridocarbazole (OPC): selective binding to DNA and polynucleotides.

    abstract::We have investigated some properties related to interaction with DNA and recognition of AT-rich sequences of netropsin-oxazolopyridocarbazole (Net-OPC) (Mrani et al., 1990), which is a hybrid groove-binder-intercalator. The hybrid molecule Net-OPC binds to poly[d(A-T)] at two different sites with Kapp values close to ...


    pub_type: 杂志文章


    authors: Subra F,Carteau S,Pager J,Paoletti J,Paoletti C,Auclair C,Mrani D,Gosselin G,Imbach JL

    更新日期:1991-02-12 00:00:00

  • Solution-state structure of the Dewar pyrimidinone photoproduct of thymidylyl-(3'----5')-thymidine.

    abstract::The preparation, spectroscopic investigation, structure determination, conformational analysis, and modeling of the Dewar pyrimidinone photoproduct of thymidylyl-(3'----5')-thymidine, previously referred to as TpT3 [Johns, H. E., Pearson, M. L., LeBlanc, J. C., & Heilleiner, C. W. (1964) J. Mol. Biol. 9, 503-524], is ...


    pub_type: 杂志文章


    authors: Taylor JS,Garrett DS,Cohrs MP

    更新日期:1988-09-20 00:00:00

  • A reexamination of the nucleotide incorporation fidelity of DNA polymerases.

    abstract::Intensive study has been devoted to understanding the kinetic and structural bases underlying the exceptionally high fidelity (low error frequencies) of the typical DNA polymerase. Commonly proposed explanations have included (i) the concept of fidelity check points, in which the correctness of a nascent base pair mat...


    pub_type: 杂志文章,评审


    authors: Showalter AK,Tsai MD

    更新日期:2002-08-27 00:00:00

  • An N-terminal three-helix fragment of the exchangeable insect apolipoprotein apolipophorin III conserves the lipid binding properties of wild-type protein.

    abstract::Apolipophorin III (apoLp-III) from the greater wax moth Galleria mellonella is an exchangeable insect apolipoprotein that consists of five amphipathic alpha-helices, sharing high sequence identity with apoLp-III from the sphinx moth Manduca sexta whose structure is available. To define the minimal requirement for apoL...


    pub_type: 杂志文章


    authors: Dettloff M,Weers PM,Niere M,Kay CM,Ryan RO,Wiesner A

    更新日期:2001-03-13 00:00:00

  • Oxygen blocks the reaction of the FixL-FixJ complex with ATP but does not influence binding of FixJ or ATP to FixL.

    abstract::The RmFixL-RmFixJ oxygen signal transduction system ensures that a cascade of the Sinorhizobium meliloti nitrogen fixation genes is induced as the concentration of O2 drops below 50 microM in symbiotic nodules. Deoxy-RmFixL is a histidine protein kinase that catalyzes a phosphoryl transfer from ATP to the aspartate 54...


    pub_type: 杂志文章


    authors: Sousa EH,Gonzalez G,Gilles-Gonzalez MA

    更新日期:2005-11-22 00:00:00

  • A new type of DNA minor-groove complex: carbazole dication-DNA interactions.

    abstract::The effect of opportunistic infections (OI) on immune-compromised populations has been known for decades, but the recent AIDS epidemic has sparked renewed interest in the development of new anti-OI agents. The mechanism of action of a series of cationic unfused-aromatic anti-OI drugs is believed to involve binding of ...


    pub_type: 杂志文章


    authors: Tanious FA,Ding D,Patrick DA,Tidwell RR,Wilson WD

    更新日期:1997-12-09 00:00:00

  • Intercalating polycyclic aromatic hydrocarbon-DNA adducts poison DNA religation by Vaccinia topoisomerase and act as roadblocks to digestion by exonuclease III.

    abstract::Polycyclic aromatic hydrocarbon (PAH)-DNA adducts pervert the execution or fidelity of enzymatic DNA transactions and cause mutations and cancer. Here, we examine the effects of intercalating PAH-DNA adducts on the religation reaction of vaccinia DNA topoisomerase, a prototypal type IB topoisomerase (TopIB), and the 3...


    pub_type: 杂志文章


    authors: Yakovleva L,Handy CJ,Yagi H,Sayer JM,Jerina DM,Shuman S

    更新日期:2006-06-20 00:00:00

  • Streptomyces wadayamensis MppP Is a Pyridoxal 5'-Phosphate-Dependent L-Arginine α-Deaminase, γ-Hydroxylase in the Enduracididine Biosynthetic Pathway.

    abstract::L-Enduracididine (L-End) is a nonproteinogenic amino acid found in a number of bioactive peptides, including the antibiotics teixobactin, enduracidin, and mannopeptimycin. The potent activity of these compounds against antibiotic-resistant pathogens like MRSA and their novel mode of action have garnered considerable i...


    pub_type: 杂志文章


    authors: Han L,Schwabacher AW,Moran GR,Silvaggi NR

    更新日期:2015-12-01 00:00:00

  • Preferential assembly of the tropomyosin heterodimer: equilibrium studies.

    abstract::Thermal unfolding/refolding studies of the three tropomyosin dimers, alpha alpha, alpha beta, and beta beta, from chicken gizzard muscle were performed to explain the preferential assembly of alpha- and beta-tropomyosin subunits into heterodimers, alpha beta [Lehrer, S. S., & Qian, Y. (1989) J. Biol. Chem. 265, 1134]....


    pub_type: 杂志文章


    authors: Lehrer SS,Stafford WF 3rd

    更新日期:1991-06-11 00:00:00

  • Effect of sequence on the conformation of DNA holliday junctions.

    abstract::Structures of the DNA sequences d(CCGGCGCCGG) and d(CCAGTACbr(5)UGG) are presented here as four-way Holliday junctions in their compact stacked-X forms, with antiparallel alignment of the DNA strands. Thus, the ACC-trinucleotide motif, previously identified as important for stabilizing the junction, is now extended to...


    pub_type: 杂志文章


    authors: Hays FA,Vargason JM,Ho PS

    更新日期:2003-08-19 00:00:00

  • Dissection of porphyrin-induced conformational dynamics in the heme biosynthesis enzyme ferrochelatase.

    abstract::Human ferrochelatase (EC catalyzes the insertion ferrous iron into protoporphyrin IX as the last step in heme biosynthesis, an essential process to most organisms given the vast intracellular functions of heme. Even with multiple ferrochelatase structures available, the exact mechanism for iron insertion int...


    pub_type: 杂志文章


    authors: Asuru AP,An M,Busenlehner LS

    更新日期:2012-09-11 00:00:00

  • Spectroscopic and kinetic studies of lipases solubilized in reverse micelles.

    abstract::The conformation and activity of three different lipases have been studied in reverse micelles formed by sodium bis(2-ethylhexyl) sulfosuccinate (AOT) in isooctane. In the case of human pancreatic lipase, the conformation of the polypeptide chain--as judged from far-UV circular dichroism measurements--is only slightly...


    pub_type: 杂志文章


    authors: Walde P,Han D,Luisi PL

    更新日期:1993-04-20 00:00:00

  • Polyamide nucleic acid targeted to the primer binding site of the HIV-1 RNA genome blocks in vitro HIV-1 reverse transcription.

    abstract::We report here that polyamide nucleic acid (PNA) as well as a polyamide nucleic acid-DNA chimera complementary to the primer binding site of the HIV-1 genome can completely block priming by tRNA3Lys and consequently the in vitro initiation of reverse transcription by HIV-1 RT. Conventional heating and cooling is not r...


    pub_type: 杂志文章


    authors: Lee R,Kaushik N,Modak MJ,Vinayak R,Pandey VN

    更新日期:1998-01-20 00:00:00

  • Comparative Analysis of CPI-Motif Regulation of Biochemical Functions of Actin Capping Protein.

    abstract::The heterodimeric actin capping protein (CP) is regulated by a set of proteins that contain CP-interacting (CPI) motifs. Outside of the CPI motif, the sequences of these proteins are unrelated and distinct. The CPI motif and surrounding sequences are conserved within a given protein family, when compared to those of o...


    pub_type: 杂志文章


    authors: McConnell P,Mekel M,Kozlov AG,Mooren OL,Lohman TM,Cooper JA

    更新日期:2020-03-24 00:00:00

  • Hydrogen-deuterium substitution and solvent effects on the nitrogen-15 nuclear magnetic resonance of gramicidin S: evaluation of secondary structure.

    abstract::Complete assignments of nitrogen-15 resonances of gramicidin S have been made in dimethyl sulfoxide, trifluoroethanol, and in a solvent mixture of dimethyl sulfoxide (50%) and methanol (50%). The assignments are achieved by utilizing the secondary structure of gramicidin S, by comparing the nitrogen-15 spectrum of gra...


    pub_type: 杂志文章


    authors: Khaled MA,Urry DW,Sugano H,Miyoshi M,Izumiya N

    更新日期:1978-06-27 00:00:00

  • Enzyme Architecture: A Startling Role for Asn270 in Glycerol 3-Phosphate Dehydrogenase-Catalyzed Hydride Transfer.

    abstract::The side chains of R269 and N270 interact with the phosphodianion of dihydroxyacetone phosphate (DHAP) bound to glycerol 3-phosphate dehydrogenase (GPDH). The R269A, N270A, and R269A/N270A mutations of GPDH result in 9.1, 5.6, and 11.5 kcal/mol destabilization, respectively, of the transition state for GPDH-catalyzed ...


    pub_type: 杂志文章


    authors: Reyes AC,Amyes TL,Richard JP

    更新日期:2016-03-15 00:00:00

  • Localization of the factor IX propeptide binding site on recombinant vitamin K dependent carboxylase using benzoylphenylalanine photoaffinity peptide inactivators.

    abstract::The propeptide binding/activation site on the vitamin K dependent carboxylase has been localized to a region of carboxylase between residues Arg +50 and Glu +225 by photoinactivation studies using [125I]tyrosyl-labeled benzoylphenylalanine (Bpa)-containing analogs of proFIX19, a peptide containing residues -18 to +1 o...


    pub_type: 杂志文章


    authors: Yamada M,Kuliopulos A,Nelson NP,Roth DA,Furie B,Furie BC,Walsh CT

    更新日期:1995-01-17 00:00:00

  • Determination of Fe-CO geometry in the subunits of carbonmonoxy hemoglobin M Boston using femtosecond infrared spectroscopy.

    abstract::We have undertaken ultrafast infrared (IR) spectroscopic studies in order to elucidate the geometry of bound CO in the alpha and beta subunits of hemoglobin (Hb) M Boston 13CO. Hb M Boston is a mutant human Hb in which the distal histidine in the alpha subunits is replaced by a tyrosine. The IR absorptions of bound 13...


    pub_type: 杂志文章


    authors: Lian T,Locke B,Kitagawa T,Nagai M,Hochstrasser RM

    更新日期:1993-06-08 00:00:00

  • Minor groove binding compounds that jump a gc base pair and bind to adjacent AT base pair sites.

    abstract::Most A/T specific heterocyclic diamidine derivatives need at least four A/T base pairs for tight binding to the DNA minor groove. Addition of a GC base pair to A/T sequences typically causes a large decrease in binding constant. The ability to target biologically important sequences of DNA could be significantly incre...


    pub_type: 杂志文章


    authors: Rahimian M,Kumar A,Say M,Bakunov SA,Boykin DW,Tidwell RR,Wilson WD

    更新日期:2009-02-24 00:00:00

  • Characterizing the response of calcium signal transducers to generated calcium transients.

    abstract::Cellular Ca2+ transients and Ca2+-binding proteins regulate physiological phenomena as diverse as muscle contraction, neurosecretion, and cell division. When Ca2+ is rapidly mixed with slow Ca2+ chelators, EGTA, or Mg2+/EDTA, artificial Ca2+ transients (ACTs) of varying duration (0.1-50 ms half-widths (hws)) and ampli...


    pub_type: 杂志文章


    authors: Davis JP,Tikunova SB,Walsh MP,Johnson JD

    更新日期:1999-03-30 00:00:00

  • Structure of the Rhodobacter sphaeroides light-harvesting 1 beta subunit in detergent micelles.

    abstract::The light harvesting 1 antenna (LH1) complex from Rhodobacter sphaeroides funnels excitation energy to the photosynthetic reaction center. Our ultimate goal is to build up the structure of LH1 from structures of its individual subunits, much as the antenna can self-assemble from its components in membrane-mimicking de...


    pub_type: 杂志文章


    authors: Sorgen PL,Cahill SM,Krueger-Koplin RD,Krueger-Koplin ST,Schenck CC,Girvin ME

    更新日期:2002-01-08 00:00:00

  • In vitro biosynthesis of a decasaccharide prototype of multiply branched polylactosaminoglycan backbones.

    abstract::Multiply branched polylactosaminoglycans are expressed in glycoproteins and glycolipids of many cells. Interest in their biology stems from their abundant expression in early embryonal cells and from their ability to carry multiple lectin-binding determinants, which makes them prominent ligands and antagonists of cell...


    pub_type: 杂志文章


    authors: Leppanen A,Salminen H,Zhu Y,Maaheimo H,Helin J,Costello CE,Renkonen O

    更新日期:1997-06-10 00:00:00

  • Resonance raman analysis of chromophore structure in the lumi-R photoproduct of phytochrome.

    abstract::Resonance Raman vibrational spectra of the Pr, lumi-R, and Pfr forms of phytochrome have been obtained using low-temperature trapping and room temperature flow techniques in conjunction with shifted-excitation Raman difference spectroscopy (SERDS). The Pr to lumi-R photoconversion exhibits a thermal barrier and is com...


    pub_type: 杂志文章


    authors: Andel F 3rd,Lagarias JC,Mathies RA

    更新日期:1996-12-17 00:00:00

  • Chemical modification of alpha-subunit tryptophan residues in Schizosaccharomyces pombe mitochondrial F1 adenosine 5'-triphosphatase: differential reactivity and role in activity.

    abstract::Chemical modification of mitochondrial F1-ATPase from Schizosaccharomyces pombe by the tryptophan-specific reagent N-bromosuccinimide (NBS) at pH 5.0 in the presence of 20% glycerol produced a characteristic lowering in both enzyme absorbance at 280 nm and intrinsic fluorescence at 332 nm that varied with NBS/F1 molar...


    pub_type: 杂志文章


    authors: Divita G,Jault JM,Gautheron DC,Di Pietro A

    更新日期:1993-02-02 00:00:00

  • Mechanism-based inactivation of P450 2A6 by furanocoumarins.

    abstract::Several furanocoumarins were tested for their ability to inhibit human P450 2A6 activity. The metabolites and conjugates formed from these furanocoumarins after incubation with reconstituted purified P450 2A6 in the absence and presence of exogenous nucleophiles were characterized by UV and LC/ESI-MS/MS analysis. The ...


    pub_type: 杂志文章


    authors: Koenigs LL,Trager WF

    更新日期:1998-07-14 00:00:00

  • Environmental effects on formation and photoreaction of the M412 photoproduct of bacteriorhodopsin: implications for the mechanism of proton pumping.

    abstract::Photochemical studies of the effects of temperature, pH, and dehydration on the formation and back photoreaction of the M412 intermediate in the photocycle of light-adapted bacteriorhodopsin (bR570) are carried out. Continuous illumination experiments in the range between -40 and -90 degrees C indicate that at low tem...


    pub_type: 杂志文章


    authors: Kalisky O,Ottolenghi M,Honig B,Korenstein R

    更新日期:1981-02-03 00:00:00

  • Energy dependent hydrogen ion accumulation in submitochondrial particles.

    abstract::The fluorescence quenching of 9-aminoacridine (9AA) in suspension of beef heart EDTA submitochondrial particles was studied and was used to calculate the pH gradient between these particles and the medium. This pH gradient, which is energy dependent, is also dependent strongly on the presence of anion species in the m...


    pub_type: 杂志文章


    authors: Rottenberg H,Lee CP

    更新日期:1975-06-17 00:00:00