The RESID Database of protein structure modifications: 2000 update

Garavelli, John S.

doi:10.1093/nar/28.1.209

Cited by 15 publications

(9 citation statements)

References 4 publications

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“…Regulatory peptides such as gonadotropin‐releasing hormone (GnRH), thyrotropin‐releasing hormone (TRH) and neurotensin, and the cytokines MCP‐1–4, require N‐terminal pyroglutamate in order to exert their respective biological functions [1,2]. Early studies have suggested that the formation of pyroglutamate at the N‐terminus of Gln 1 peptides was a spontaneous reaction [3].…”

Section: Introductionmentioning

confidence: 99%

Glutaminyl cyclases unfold glutamyl cyclase activity under mild acid conditions

et al. 2004

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N-terminal pyroglutamate (pGlu) formation from glutaminyl precursors is a posttranslational event in the processing of bioactive neuropeptides such as thyrotropin-releasing hormone and neurotensin during their maturation in the secretory pathway. The reaction is facilitated by glutaminyl cyclase (QC), an enzyme highly abundant in mammalian brain. Here, we describe for the ¢rst time that human and papaya QC also catalyze N-terminal glutamate cyclization. Surprisingly, the enzymatic Glu 1 conversion is favored at pH 6.0 while Gln 1 conversion occurs with an optimum at pH 8.0. This unexpected ¢nding might be of importance for deciphering the events leading to deposition of highly toxic pyroglutamyl peptides in amyloidotic diseases. ß 2004 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.

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Section: Introductionmentioning

confidence: 99%

Glutaminyl cyclases unfold glutamyl cyclase activity under mild acid conditions

et al. 2004

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“…Glutaminyl cyclase (QC, EC 2.3.2.5) catalyzes the intramolecular cyclization of N-terminal glutamine residues to pyroglutamic acid (pGlu) under liberation of ammonia. − QC is located in mammalian pituitary, hypothalamus, other parts of the brain, adrenal medulla, and B lymphocytes. , Some peptide hormones, such as tyrotropin releasing hormone (TRH) and gonadotropin releasing hormone (GnRH), require the pGlu on the N-terminus for their biological activity. , The colocalization of QC and its putative products within the regulated secretory pathway suggests a potential involvement of the enzyme in the final maturation of these peptide hormones . The recently described ability of human QC to convert the N-terminal glutamate of the peptide Glu 3 -Aβ(3−21), of the amyloid precursor protein (APP), into the respective pGlu 3 -Aβ(3−21) in an in vitro experiment suggests QC's possible involvement in the initiation of the neurotoxic plaque formation in Alzheimer's disease (AD) .…”

Section: Introductionmentioning

confidence: 99%

“…1,4 Some peptide hormones, such as tyrotropin releasing hormone (TRH) and gonadotropin releasing hormone (GnRH), require the pGlu on the N-terminus for their biological activity. 5,6 The colocalization of QC and its putative products within the regulated secretory pathway suggests a potential involvement of the enzyme in the final maturation of these peptide hormones. 7 The recently described ability of human QC to convert the N-terminal glutamate of the peptide Glu 3 -Aβ (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21), of the amyloid precursor protein (APP), into the respective pGlu 3 -Aβ (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21) in an in vitro experiment suggests QC's possible involvement in the initiation of the neurotoxic plaque formation in Alzheimer's disease (AD).…”

Section: Introductionmentioning

confidence: 99%

The First Potent Inhibitors for Human Glutaminyl Cyclase: Synthesis and Structure−Activity Relationship

et al. 2005

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The first effective inhibitors for human glutaminyl cyclase (QC) are described. The structures are developed by applying a ligand-based optimization approach starting from imidazole. Screening of derivatives of that heterocycle led to compounds of the imidazol-1-yl-alkyl thiourea type as a lead scaffold. A library of thiourea derivatives was synthesized, resulting in an inhibitory improvement by 2 orders of magnitude, leading to 1-(3-(1H-imidazol-1-yl)propyl)-3-(3,4-dimethoxyphenyl)thiourea as a potent inhibitor. Systematic exploitation of the scaffold revealed a strong impact on the inhibitory efficacy and resulted in the development of imidazole-propyl-thioamides as another new class of potent inhibitors. A flexible alignment of the most potent compounds of the thioamide and thiourea class and a QC substrate revealed a good match of characteristic features of the molecules, which suggests a similar binding mode of both inhibitors and the substrate to the active site of QC.

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“…They may also be involved in disease processes. We have mapped Protein Modifications (PMs) in the PDB to the RESID database of PMs (18,19) and the associated Protein Modifications Ontology PSI-MOD (20). PM definitions and the software to identify them are available from the BioJava project (21) (https://github.com/biojava/biojava/tree/master/biojava-modfinder).…”

Section: New Website Featuresmentioning

confidence: 99%

OUP accepted manuscript

Rose

Prlić

Altunkaya

et al. 2016

Nucleic Acids Research

535

233

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The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB, http://rcsb.org), the US data center for the global PDB archive, makes PDB data freely available to all users, from structural biologists to computational biologists and beyond. New tools and resources have been added to the RCSB PDB web portal in support of a ‘Structural View of Biology.’ Recent developments have improved the User experience, including the high-speed NGL Viewer that provides 3D molecular visualization in any web browser, improved support for data file download and enhanced organization of website pages for query, reporting and individual structure exploration. Structure validation information is now visible for all archival entries. PDB data have been integrated with external biological resources, including chromosomal position within the human genome; protein modifications; and metabolic pathways. PDB-101 educational materials have been reorganized into a searchable website and expanded to include new features such as the Geis Digital Archive.

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The RESID Database of protein structure modifications: 2000 update

Cited by 15 publications

References 4 publications

Glutaminyl cyclases unfold glutamyl cyclase activity under mild acid conditions

Glutaminyl cyclases unfold glutamyl cyclase activity under mild acid conditions

The First Potent Inhibitors for Human Glutaminyl Cyclase: Synthesis and Structure−Activity Relationship

OUP accepted manuscript

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