Abstract：
:Type 1 diabetes (T1D) is an autoimmune disease characterized by an insulin deficiency. Ever since the discovery of insulin almost 100 years ago, patients with T1D have relied on multiple daily insulin injections to survive an otherwise deadly disease. Despite decades of research and clinical trials, no treatment exists yet to prevent or cure T1D. A recent prevention trial using the anti-CD3 antibody teplizumab in individuals at a high risk of developing T1D has provided the first piece of evidence that a safe and transient intervention may be able to delay disease. In this Perspective, we review the 40-year long history of anti-CD3 and discuss how this antibody became a candidate for the treatment of autoimmune diabetes. The path that leads to its use in this latest clinical trial for T1D has been winding and strewn with setbacks. The molecular actions of the anti-CD3 antibody that target T lymphocytes are well-understood, but its systemic effect on immune function has proven more difficult to unravel. Moreover, preclinical data suggested that the utility of anti-CD3 for the prevention of T1D may be limited. However, the latest clinical data are encouraging and exemplify how a basic discovery can, decades later and with much perseverance, become a promising therapeutic candidate.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Gaglia J,Kissler Sdoi
10.1021/acs.biochem.9b00707subject
Has Abstractpub_date
2019-10-08 00:00:00pages
4107-4111issue
40eissn
0006-2960issn
1520-4995journal_volume
58pub_type
杂志文章,评审相关文献
BIOCHEMISTRY文献大全abstract：:The structural protein nonerythroid alpha spectrin (alphaIISp) plays a role in the repair of DNA interstrand cross-links and is deficient in cells from patients with Fanconi anemia (FA), in which there is a defect in ability to repair such cross-links. We have proposed a model in which alphaIISp, whose stability is de...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi801483u
更新日期：2009-01-20 00:00:00
abstract：:The ligand-binding dynamics and the reaction with O(2) of the fully (five-electron) reduced cytochrome caa(3) from the thermohalophilic bacterium Rhodothermus (R.) marinus were investigated. The enzyme is a proton pump which has all the residues of the proton-transfer pathways found in the mitochondrial-like enzymes c...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi010344h
更新日期：2001-09-04 00:00:00
abstract：:PsbU is a lumenal peripheral protein in the photosystem II (PS II) complex of cyanobacteria and red algae. It is thought that PsbU is replaced functionally by PsbP or PsbQ in plant chloroplasts. After the discovery of PsbP and PsbQ homologues in cyanobacterial PS II [Thornton et al. (2004) Plant Cell 16, 2164-2175], w...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi047539k
更新日期：2005-09-13 00:00:00
abstract：:The relaxin-like factor (RLF) is a circulating hormone that is synthesized in the gonads of mammals and released into the bloodstream. The distribution of its receptor and a trace of cross-reactivity to relaxin receptors implied that this relatively new factor is more relaxin- than insulin-like. The chemical synthesis...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi982687u
更新日期：1999-03-09 00:00:00
abstract：:The causes of the salting-in of beta-lactoglobulin by glycine and NaCl, a solubility behavior contrary to expectations, were probed by a detailed study of the interactions between these solvent components and the protein. The preferential interactions of beta-lactoglobulin with solvent components in aqueous glycine an...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00390a038
更新日期：1987-08-11 00:00:00
abstract：:The E2 protein of papillomavirus is the key regulator of viral transcription and replication. Dimerization, which takes place via its conserved C-terminal DNA-binding domain (DBD), is critical for these functions. The presence and conservation of two histidines (H290 and H320) at or near the dimer interface suggests t...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi0611255
更新日期：2007-02-06 00:00:00
abstract：:Snake venom contains a number of the hemostatically active C-type lectin-like proteins, which affect the interaction between von Willebrand factor (vWF) and the platelet glycoprotein (GP) Ib or platelet receptor to inhibit/induce platelet activation. Flavocetin-A (FL-A) is a high-molecular mass C-type lectin-like prot...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi992134z
更新日期：2000-02-29 00:00:00
abstract：:A wide range of two-dimensional 1H NMR experiments have been used to completely assign the 500-MHz 1H NMR spectrum of recombinant Ca2+-saturated bovine calbindin D9k (76 amino acids, Mr = 8500). In solution, calbindin D9k exists as an equilibrium mixture of isoforms with trans (75%) and cis (25%) isomers of the peptid...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00443a043
更新日期：1989-08-22 00:00:00
abstract：:These investigations characterize the covalent binding of reactive products of prostaglandin H-synthases (PGHSs) to the enzyme and to other molecules. The intermediate product of oxygenation of arachidonic acid by the PGHSs, prostaglandin (PG) H2, undergoes rearrangement to the highly reactive gamma-keto aldehydes, le...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi002629k
更新日期：2001-06-12 00:00:00
abstract：:The Fv fragment, a univalent antigen-binding unit with a molecular weight of 25,000, has successfully been prepared in high yield by limited proteolysis with clostripain of a short-chain mouse IgG2a anti-dansyl monoclonal antibody in which the entire CH1 domain is deleted [Igarashi, T., Sato, M., Takio, K., Tanaka, T....
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00225a016
更新日期：1991-03-19 00:00:00
abstract：:Limited digestion of polysomal RNA with pancreatic ribonuclease releases a structure consisting of poly(A) associated with other polyribonucleotide sequences. This complex can be purified by oligo(dT)-cellulose chromatography. Heating for formamide treatment causes the dissociation of fragments free of poly(A) from th...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00686a024
更新日期：1975-07-29 00:00:00
abstract：:The reaction of Pseudomonas fluorescens kynureninase with L-kynurenine and L-alanine has been examined using rapid-scanning stopped-flow spectrophotometry. Mixing kynureninase with 0.5 mM L-kynurenine results in formation of a quinonoid intermediate, with lambdamax = 494 nm, within the dead time (ca. 2 ms) of the stop...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi980066v
更新日期：1998-06-16 00:00:00
abstract：:We have determined the nucleotide sequence and the derived amino acid sequence of the phosphoprotein-encoding region of the chicken vitellogenin III gene. The sequence of this minor vitellogenin could be aligned with exon 22 up to exon 27 of the previously sequenced major vitellogenin II gene (van het Schip et al., 19...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00432a034
更新日期：1989-03-21 00:00:00
abstract：:Single-tryptophan-containing mutants of low adenylation state Escherichia coli glutamine synthetase (wild type has two tryptophans at positions 57 and 158) have been constructed and studied by multifrequency phase/modulation fluorescence spectroscopy. The W57L mutant (retains tryptophan at residue 158) and the W158S m...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00228a008
更新日期：1991-04-09 00:00:00
abstract：:The surface immobilization methods that allowed single-molecule motility experiments with native kinesin have not worked with the ncd motor protein and other kinesin-related motors. To solve this problem, a surfactant (Pluronic F108) was chemically modified with the metal-chelating group nitrilotriacetic acid (NTA) to...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi9829175
更新日期：1999-04-20 00:00:00
abstract：:The folding and unfolding rates of the small protein, barstar, have been monitored using stopped-flow measurements of intrinsic tryptophan fluorescence at 25 degrees C, pH 8.5, and have been compared over a wide range of urea and guanidine hydrochloride (GdnHCl) concentrations. When the logarithms of the rates of fold...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi011494v
更新日期：2002-02-05 00:00:00
abstract：:The complex of dioldehydrase with adenosylcobalamin (coenzyme B12) and potassium ion reacts with molecular oxygen in the absence of a substrate to oxidize coenzyme and inactivate the complex. In this article, high performance liquid chromatography and mass spectral analysis are used to identify the nucleoside products...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi700078z
更新日期：2007-06-19 00:00:00
abstract：:The purified ATPase of sarcoplasmic reticulum was covalently labeled with N-iodoacetyl-N'-(5-sulfo-1-naphthyl)ethylenediamine (1,5-IAEDANS) or with iodoacetamidofluorescein (IAF). In reconstituted vesicles containing both types of ATPase molecules fluorescence energy transfer was observed from the IAEDANS (donor) to t...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00626a003
更新日期：1977-04-05 00:00:00
abstract：:The X-ray crystal structure of the complex of the B-DNA dodecamer CGCGAATTCGCG with the antitumor drug netropsin has been reexamined to locate the drug accurately for computer-based drug design. The optimum solution is with the drug centered in the AATT region of the minor groove, making three good bifurcated hydrogen...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00015a009
更新日期：1995-04-18 00:00:00
abstract：:The binding of the codon UUC to the isolated anticodon loop of tRNAPhe (yeast) has been studied as a model of codon recognition by a simple adaptor. Fluorescence titrations demonstrate that UUC binds to the isolated anticodon loop with an equilibrium constant of 1.4 X 10(3) M-1 (at 7.2 degrees C). Equilibrium sediment...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00369a005
更新日期：1986-10-21 00:00:00
abstract：:Pectate lyase C (pelC) was the first protein in which the parallel beta-helix structure was recognized. The unique features of parallel beta-helix-containing proteins-a relatively simple topology and unusual interactions among side chains-make pelC an interesting protein to study with respect to protein folding. In th...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi001900v
更新日期：2000-12-26 00:00:00
abstract：:Specific lysine residues on the ubiquitin surface were selected during the course of evolution to form different polyubiquitin chain structures that signal diverse cellular processes. A vast number of ubiquitin receptors specifically recognize and decode the signals conferred by these polyubiquitin chains. The mechani...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/acs.biochem.5b00498
更新日期：2015-08-04 00:00:00
abstract：:The peptide hormone bradykinin exerts important biological functions by binding to and activating bradykinin B2 receptors. B2 receptors belong to the seven transmembrane domain (7TM) receptor family. Cloning of the cDNA sequences for the rat, human, and mouse bradykinin B2 receptor revealed several in-frame AUG triple...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi9601060
更新日期：1996-06-11 00:00:00
abstract：:The structure of an active mutant of (S)-mandelate dehydrogenase (MDH-GOX2) from Pseudomonas putida has been determined at 2.15 A resolution. The membrane-associated flavoenzyme (S)-mandelate dehydrogenase (MDH) catalyzes the oxidation of (S)-mandelate to give a flavin hydroquinone intermediate which is subsequently r...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi010938k
更新日期：2001-08-21 00:00:00
abstract：:Rat alpha- and beta-parvalbumins have distinct monovalent cation-binding properties [Henzl et al. (2000) Biochemistry 39, 5859-5867]. Beta binds two Na(+) or one K(+), and alpha binds one Na(+) and no K(+). Ca(2+) abolishes these binding events, suggesting that the monovalent ions occupy the EF-hand motifs. This study...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi035890k
更新日期：2004-03-16 00:00:00
abstract：:Gamma-aminobutyric acid type A receptors (GABA(A) receptors) are ligand-gated chloride channels that play a central role in signal transmission within the mammalian central nervous system. Compounds that modulate specific GABA(A) receptor subtypes containing the delta-subunit are scarce but would be valuable research ...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi100119t
更新日期：2010-06-15 00:00:00
abstract：:It has been suggested that dimeric tubulin can participate in the signal transduction process through its association with the GTP-binding (G) proteins Gs and Gi1. Using the photoaffinity GTP analog, azidoanilido-GTP, it has been shown that the transfer of nucleotide from tubulin to G alpha s and G alpha i1 is the key...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00198a052
更新日期：1994-08-16 00:00:00
abstract：:Site-directed mutants of human carbonic anhydrase III were used to examine the role of Thr-199 and its interaction with Phe-198 in the catalyzed hydration of CO2. Threonine-199 is a hydrogen bond acceptor for the zinc-bound water, and Phe-198 forms part of the hydrophobic side of the active-site cavity of carbonic anh...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00082a004
更新日期：1993-08-10 00:00:00
abstract：:The dependence of the activity of recombinant activated human protein C (r-APC) on each of its nine gamma-carboxyglutamic (Gla) residues (sequence positions 6, 7, 14, 16, 19, 20, 25, 26, and 29) has been assessed in purified systems and in plasma using r-mutants in which each Gla residue of r-APC was individually alte...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00173a033
更新日期：1994-02-22 00:00:00
abstract：:Pyruvate decarboxylase (PDC) uses thiamine diphosphate as an essential cofactor to catalyze the formation of acetaldehyde on the pathway of ethanol synthesis. Here we report the crystallographic image of a prereaction intermediate of a bacterial pyruvate decarboxylase prepared by cocrystallizing the enzyme with pyruva...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi901864j
更新日期：2010-03-02 00:00:00
