当前位置： SCI文献检索 > JOURNAL OF MOLECULAR BIOLOGY期刊下所有文献 > A fibrin-specific monoclonal antibody from a designed phage display library inhibits clot formation and localizes to tumors in vivo.

A fibrin-specific monoclonal antibody from a designed phage display library inhibits clot formation and localizes to tumors in vivo.

Abstract：

:Fibrin formation from fibrinogen is a rare process in the healthy organism but is a pathological feature of thrombotic events, cancer and a wide range of inflammatory conditions. We have designed and constructed an antibody phage display library (containing 13 billion clones) for the selective recognition of the N-terminal peptide of fibrin alpha chain. The key structural feature for selective fibrin binding was a K94E mutation in the VH domain. From this library, an antibody was isolated (termed AP2), which recognizes the five N-terminal amino acids of fibrin with high affinity (Kd=44nM), but does not bind to fibrinogen. The AP2 antibody could be expressed in various formats (scFv, small immune protein and IgG) and inhibited fibrin clot formation in a concentration-dependent manner. Moreover, the AP2 antibody stained the fibrin-rich provisional stroma in solid tumors but did not exhibit any detectable staining toward normal tissues. Using a radioiodinated antibody preparation and quantitative biodistribution studies in tumor-bearing mice, AP2 was shown to selectively localize to fibrin-rich F9 murine teratocarcinomas, but not to SKRC-52 human kidney cancer xenografts. Collectively, the experiments indicate that the AP2 antibody recognizes fibrin in vitro and in vivo. The antibody may facilitate the development of fibrin-specific therapeutic agents.

journal_name

J Mol Biol

journal_title

Journal of molecular biology

authors

Putelli A,Kiefer JD,Zadory M,Matasci M,Neri D

doi

10.1016/j.jmb.2014.07.023

subject

Has Abstract

pub_date

2014-10-23 00:00:00

pages

3606-18

issue

21

eissn

0022-2836

issn

1089-8638

pii

S0022-2836(14)00371-4

journal_volume

426

pub_type

杂志文章

相关文献

JOURNAL OF MOLECULAR BIOLOGY文献大全
  • Crystal structure of the soluble domain of the major anaerobically induced outer membrane protein (AniA) from pathogenic Neisseria: a new class of copper-containing nitrite reductases.

    abstract：:The major anaerobically induced outer membrane protein (AniA) from pathogenic Neisseria gonorrhoeae is essential for cell growth under oxygen limiting conditions in the presence of nitrite and is protective against killing by human sera. A phylogenic analysis indicates that AniA is a member of a new class of copper-co...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1006/jmbi.2001.5251

    authors： Boulanger MJ,Murphy ME

    更新日期：2002-02-01 00:00:00

  • Ribosomal protein L9: a structure determination by the combined use of X-ray crystallography and NMR spectroscopy.

    abstract：:The structure of protein L9 from the Bacillus stearothernophilus ribosome has been determined at 2.5 A resolution by refinement against single crystal X-ray diffraction data with additional constraints provided by NMR data. This highly elongated protein consists of two domains separated by a nine-turn connecting helix...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1006/jmbi.1996.0696

    authors： Hoffman DW,Cameron CS,Davies C,White SW,Ramakrishnan V

    更新日期：1996-12-20 00:00:00

  • Predicting Protein-Protein Interfaces that Bind Intrinsically Disordered Protein Regions.

    abstract：:A long-standing goal in biology is the complete annotation of function and structure on all protein-protein interactions, a large fraction of which is mediated by intrinsically disordered protein regions (IDRs). However, knowledge derived from experimental structures of such protein complexes is disproportionately sma...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2019.06.010

    authors： Wong ETC,Gsponer J

    更新日期：2019-08-09 00:00:00

  • Tetrameric structure of thermostable direct hemolysin from vibrio parahaemolyticus revealed by ultracentrifugation, small-angle X-ray scattering and electron microscopy.

    abstract：:The thermostable direct hemolysin (TDH) is a major virulence factor of Vibrio parahaemolyticus. We have characterized the conformational properties of TDH by small-angle X-ray scattering (SAXS), ultracentrifugation and transmission electron microscopy. Sedimentation equilibrium and velocity studies revealed that the p...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2006.09.070

    authors： Hamada D,Higurashi T,Mayanagi K,Miyata T,Fukui T,Iida T,Honda T,Yanagihara I

    更新日期：2007-01-05 00:00:00

  • Comparison of the refined crystal structures of liganded and unliganded chicken, yeast and trypanosomal triosephosphate isomerase.

    abstract：:The refined crystal structures of chicken, yeast and trypanosomal triosephosphate isomerase (TIM) have been compared. TIM is known to exist in an "open" (unliganded) and "closed" (liganded) conformation. For chicken TIM only the refined open structure is available, whereas for yeast TIM and trypanosomal TIM refined st...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/0022-2836(92)90473-w

    authors： Wierenga RK,Noble ME,Davenport RC

    更新日期：1992-04-20 00:00:00

  • Structures of DegQ from Legionella pneumophila Define Distinct ON and OFF States.

    abstract：:HtrA (high-temperature requirement A) family proteins play important roles in protein-quality control processes in the bacterial periplasm. A common feature of all members of this family is their modular organization comprising a chymotrypsin-like protease domain and at least one PDZ (postsynaptic density of 95 kDa, d...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2015.06.023

    authors： Schubert A,Wrase R,Hilgenfeld R,Hansen G

    更新日期：2015-08-28 00:00:00

  • Detection of single-stranded DNA in scrapie-infected brain by electron microscopy.

    abstract：:The nucleic acid content of enriched preparations of mitochondria/tubulofilamentous particles from normal and scrapie-infected hamster brains were examined by electron microscopy. After spreading on collodion-coated grids circular molecules of approximately 15.7 kb corresponding in size to mitochondrial DNA (mtDNA) we...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/0022-2836(90)90369-W

    authors： Narang HK

    更新日期：1990-12-05 00:00:00

  • Probing dimerization and structural flexibility of mammalian lipoxygenases by small-angle X-ray scattering.

    abstract：:Human lipoxygenases (LOXs) and their metabolites have a great impact on human homeostasis and are of interest for targeted drug design. This goal requires detailed knowledge of their structures and an understanding of structure-function relationship. At the moment, there are two complete crystal structures for mammali...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2011.04.035

    authors： Shang W,Ivanov I,Svergun DI,Borbulevych OY,Aleem AM,Stehling S,Jankun J,Kühn H,Skrzypczak-Jankun E

    更新日期：2011-06-17 00:00:00

  • Molecular principles of the interactions of disordered proteins.

    abstract：:Thorough knowledge of the molecular principles of protein-protein recognition is essential to our understanding of protein function at the cellular level. Whereas interactions of ordered proteins have been analyzed in great detail, complexes of intrinsically unstructured/disordered proteins (IUPs) have hardly been add...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2007.07.004

    authors： Mészáros B,Tompa P,Simon I,Dosztányi Z

    更新日期：2007-09-14 00:00:00

  • Crystal structure and novel recognition motif of rho ADP-ribosylating C3 exoenzyme from Clostridium botulinum: structural insights for recognition specificity and catalysis.

    abstract：:Clostridium botulinum C3 exoenzyme inactivates the small GTP-binding protein family Rho by ADP-ribosylating asparagine 41, which depolymerizes the actin cytoskeleton. C3 thus represents a major family of the bacterial toxins that transfer the ADP-ribose moiety of NAD to specific amino acids in acceptor proteins to mod...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1006/jmbi.2000.4292

    authors： Han S,Arvai AS,Clancy SB,Tainer JA

    更新日期：2001-01-05 00:00:00

  • Pulse-chase analysis of the in vivo assembly of the bacteriophage T4 tail.

    abstract：:The in vivo assembly pathway of the complex tail of bacteriophage T4 virus was determined using pulse-chase analysis as a non-invasive alternative to the in vitro experiments previously used to map assembly. Bacteriophage T4 mutants defective in head assembly were used to infect cultures of Escherichia coli in order t...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1006/jmbi.2000.3551

    authors： Ferguson PL,Coombs DH

    更新日期：2000-03-17 00:00:00

  • Structure of selenophosphate synthetase essential for selenium incorporation into proteins and RNAs.

    abstract：:Selenophosphate synthetase (SPS) catalyzes the activation of selenide with adenosine 5'-triphosphate (ATP) to generate selenophosphate, the essential reactive selenium donor for the formation of selenocysteine (Sec) and 2-selenouridine residues in proteins and RNAs, respectively. Many SPS are themselves Sec-containing...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2008.08.042

    authors： Itoh Y,Sekine S,Matsumoto E,Akasaka R,Takemoto C,Shirouzu M,Yokoyama S

    更新日期：2009-02-06 00:00:00

  • Real-Time Single-Molecule Kinetic Analyses of AIP1-Enhanced Actin Filament Severing in the Presence of Cofilin.

    abstract：:Rearrangement of actin filaments by polymerization, depolymerization, and severing is important for cell locomotion, membrane trafficking, and many other cellular functions. Cofilin and actin-interacting protein 1 (AIP1; also known as WDR1) are evolutionally conserved proteins that cooperatively sever actin filaments....

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2018.11.010

    authors： Hayakawa K,Sekiguchi C,Sokabe M,Ono S,Tatsumi H

    更新日期：2019-01-18 00:00:00

  • Crystal structure of Hsc20, a J-type Co-chaperone from Escherichia coli.

    abstract：:Hsc20 is a 20 kDa J-protein that regulates the ATPase activity and peptide-binding specificity of Hsc66, an hsp70-class molecular chaperone. We report herein the crystal structure of Hsc20 from Escherichia coli determined to a resolution of 1.8 A using a combination of single isomorphous replacement (SIR) and multi-wa...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1006/jmbi.2000.4252

    authors： Cupp-Vickery JR,Vickery LE

    更新日期：2000-12-15 00:00:00

  • Mathematical modeling of the effects of the signal recognition particle on translation and translocation of proteins across the endoplasmic reticulum membrane.

    abstract：:The kinetics of the signal recognition particle(SRP)-mediated process of protein translocation across the endoplasmic reticulum membrane was studied by mathematical modeling and complementary experiments. The following results were obtained. (1) A model according to which SRP directs the ribosome, rather than the mRNA...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/0022-2836(87)90186-0

    authors： Rapoport TA,Heinrich R,Walter P,Schulmeister T

    更新日期：1987-06-05 00:00:00

  • A unique FGF23 with the ability to activate FGFR signaling through both αKlotho and βKlotho.

    abstract：:Three fibroblast growth factor (FGF) molecules, FGF19, FGF21, and FGF23, form a unique subfamily that functions as endocrine hormones. FGF19 and FGF21 can regulate glucose, lipid, and energy metabolism, while FGF23 regulates phosphate homeostasis. The FGF receptors and co-receptors for these three FGF molecules have b...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2012.02.027

    authors： Wu X,Weiszmann J,Ge H,Baribault H,Stevens J,Hawkins N,Vonderfecht S,Gardner J,Gupte J,Sheng J,Wang M,Li Y

    更新日期：2012-04-20 00:00:00

  • Islet amyloid polypeptide forms rigid lipid-protein amyloid fibrils on supported phospholipid bilayers.

    abstract：:Islet amyloid polypeptide (IAPP) forms fibrillar amyloid deposits in the pancreatic islets of Langerhans of patients with type 2 diabetes mellitus, and its misfolding and aggregation are thought to contribute to beta-cell death. Increasing evidence suggests that IAPP fibrillization is strongly influenced by lipid memb...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2007.11.077

    authors： Domanov YA,Kinnunen PK

    更新日期：2008-02-08 00:00:00

  • Yeast RNase III as a key processing enzyme in small nucleolar RNAs metabolism.

    abstract：:The variety of biogenesis pathways for small nucleolar RNAs (snoRNAs) reflects the diversity of their genomic organization. We have searched for yeast snoRNAs which are affected by the depletion of the yeast ortholog of bacterial RNase III, Rnt1. In a yeast strain inactivated for RNT1, almost half of the snoRNAs teste...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1006/jmbi.1998.2237

    authors： Chanfreau G,Legrain P,Jacquier A

    更新日期：1998-12-11 00:00:00

  • Determination of the pK(a) of the four Zn2+-coordinating residues of the distal finger motif of the HIV-1 nucleocapsid protein: consequences on the binding of Zn2+.

    abstract：:The nucleocapsid protein NCp7 of human immunodeficiency virus type 1 is characterized by two highly conserved CCHC motifs that bind Zn2+ strongly. To elucidate the striking pH-dependence of the apparent Zn2+-binding constants of these motifs further, we investigated, using 1H NMR, potentiometry and fluorescence spectr...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1006/jmbi.2001.4770

    authors： Bombarda E,Morellet N,Cherradi H,Spiess B,Bouaziz S,Grell E,Roques BP,Mély Y

    更新日期：2001-07-13 00:00:00

  • The human homologue of the yeast splicing factor prp6p contains multiple TPR elements and is stably associated with the U5 snRNP via protein-protein interactions.

    abstract：:An essential step of pre-mRNA spliceosome assembly is the interaction between the snRNPs U4/U6 and U5, to form the [U4/U6.U5] tri-snRNP. While the tri-snRNP protein Prp6p appears to play an important role for tri-snRNP formation in yeast, little is known about the interactions that connect the two snRNP particles in h...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1006/jmbi.2000.3685

    authors： Makarov EM,Makarova OV,Achsel T,Lührmann R

    更新日期：2000-05-12 00:00:00

  • Exhaustive enumeration of protein domain families.

    abstract：:Domains are considered as the basic units of protein folding, evolution, and function. Decomposing each protein into modular domains is thus a basic prerequisite for accurate functional classification of biological molecules. Here, we present ADDA, an automatic algorithm for domain decomposition and clustering of all ...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/s0022-2836(03)00269-9

    authors： Heger A,Holm L

    更新日期：2003-05-02 00:00:00

  • Aromatic-aromatic interactions and protein stability. Investigation by double-mutant cycles.

    abstract：:The side-chains of phenylalanine and tyrosine residues in proteins are frequently found to be involved in pairwise interactions. These occur both within repeating elements of secondary structure and in tertiary and quaternary interactions. It has been suggested that they are important in protein folding and stability,...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/0022-2836(91)90725-l

    authors： Serrano L,Bycroft M,Fersht AR

    更新日期：1991-03-20 00:00:00

  • The crystal structure of Pyrococcus furiosus UMP kinase provides insight into catalysis and regulation in microbial pyrimidine nucleotide biosynthesis.

    abstract：:UMP kinase (UMPK), the enzyme responsible for microbial UMP phosphorylation, plays a key role in pyrimidine nucleotide biosynthesis, regulating this process via feed-back control and via gene repression of carbamoyl phosphate synthetase (the first enzyme of the pyrimidine biosynthesis pathway). We present crystal stru...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2005.07.045

    authors： Marco-Marín C,Gil-Ortiz F,Rubio V

    更新日期：2005-09-16 00:00:00

  • Structural properties of a collagenous heterotrimer that mimics the collagenase cleavage site of collagen type I.

    abstract：:Collagens contain sequence- and conformation-dependent epitopes responsible for their digestion by collagenases at specific loci. A synthetic heterotrimer construct containing the collagenase cleavage site of collagen type I was found to mimic perfectly native collagen in terms of selectivity and mode of enzymatic deg...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/S0022-2836(02)00365-0

    authors： Fiori S,Saccà B,Moroder L

    更新日期：2002-06-21 00:00:00

  • Localization of ammonium ions in the minor groove of DNA duplexes in solution and the origin of DNA A-tract bending.

    abstract：:Monovalent cation binding sites on nucleic acids in solution can be localized using the isotopically labeled ammonium ion (15NH4+) as a probe in high resolution NMR spectroscopy experiments. The application of this technique to a series of DNA duplexes reveals a preference for the binding of ammonium cations in the mi...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1006/jmbi.1998.2513

    authors： Hud NV,Sklenár V,Feigon J

    更新日期：1999-02-26 00:00:00

  • Halogenated benzenes bound within a non-polar cavity in T4 lysozyme provide examples of I...S and I...Se halogen-bonding.

    abstract：:We showed earlier that the mutation of Leu99 to alanine in bacteriophage T4 lysozyme creates an internal cavity of volume approximately 150 A(3) that binds benzene and a variety of other ligands. As such, this cavity provides an excellent target to study protein-ligand interaction. Here, we use low-temperature crystal...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2008.10.086

    authors： Liu L,Baase WA,Matthews BW

    更新日期：2009-01-16 00:00:00

  • Effect of single DNA lesions on in vitro replication with DNA polymerase III holoenzyme. Comparison with other polymerases.

    abstract：:In the present work, we have studied in vitro replication of N-2-acetylaminofluorene (AAF) or cis-diamminedichloroplatinum II (cis-DDP) single modified DNA templates. We used the holoenzyme (pol III HE) or the alpha subunit of DNA polymerase III, which is involved in SOS mutagenesis, and other DNA polymerases in order...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1006/jmbi.1994.1125

    authors： Belguise-Valladier P,Maki H,Sekiguchi M,Fuchs RP

    更新日期：1994-02-11 00:00:00

  • Positive selection of synonymous mutations in vesicular stomatitis virus.

    abstract：:Prevailing evolutionary forces are typically deduced from the pattern of differences in synonymous and non-synonymous mutations, under the assumption of neutrality in the absence of amino acid change. We determined the complete sequence of ten vesicular stomatitis virus populations evolving under positive selection. A...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2004.08.003

    authors： Novella IS,Zárate S,Metzgar D,Ebendick-Corpus BE

    更新日期：2004-10-01 00:00:00

  • The positive transcription elongation factor b is an essential cofactor for the activation of transcription by myocyte enhancer factor 2.

    abstract：:The positive transcription elongation factor b (P-TEFb), composed of cyclin-dependent kinase 9 and cyclin T1, stimulates the elongation of transcription by hyperphosphorylating the C-terminal region of RNA polymerase II. Aberrant activation of P-TEFb results in manifestations of cardiac hypertrophy in mice, suggesting...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2008.07.017

    authors： Nojima M,Huang Y,Tyagi M,Kao HY,Fujinaga K

    更新日期：2008-10-03 00:00:00

  • Homo-oligomerization domains in the lethal(2)giant larvae tumor suppressor protein, p127 of Drosophila.

    abstract：:The p127 tumor suppressor protein encoded by the lethal(2)giant larvae, l(2)gl, gene of Drosophila melanogaster forms high molecular mass complexes consisting predominantly of p127 molecules. To determine whether p127 can self-assemble in the absence of other binding factors, we analyzed the size of in vitro synthesiz...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1006/jmbi.1996.0656

    authors： Jakobs R,de Lorenzo C,Spiess E,Strand D,Mechler BM

    更新日期：1996-12-06 00:00:00