The X-ray structure of human calbindin-D28K: an improved model

Noble, James W.; Almalki, Rehab; Roe, S. Mark; Wagner, Armin; Duman, Ramona; Atack, John

doi:10.1107/s2059798318011610

Cited by 21 publications

(17 citation statements)

References 47 publications

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“…The protocol for expressing and purifying calbindin-D28k was derived from [52] with minor modifications. We purchased an already cloned into pET15b codon-optimized cDNA for CALB1 expression in E. coli, with flanking restriction sites for NcoI and BamHI (GenScript, Piscataway, NJ, USA).…”

Section: Expression and Purification Of Calbindin-d28kmentioning

confidence: 99%

Design and Experimental Evaluation of a Peptide Antagonist against Amyloid β(1–42) Interactions with Calmodulin and Calbindin-D28k

Salazar

Poejo

Mata

et al. 2022

IJMS

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Amyloid β1–42 (Aβ(1–42)) oligomers have been linked to the pathogenesis of Alzheimer’s disease (AD). Intracellular calcium (Ca2+) homeostasis dysregulation with subsequent alterations of neuronal excitability has been proposed to mediate Aβ neurotoxicity in AD. The Ca2+ binding proteins calmodulin (CaM) and calbindin-D28k, whose expression levels are lowered in human AD brains, have relevant roles in neuronal survival and activity. In previous works, we have shown that CaM has a high affinity for Aβ(1–42) oligomers and extensively binds internalized Aβ(1–42) in neurons. In this work, we have designed a hydrophobic peptide of 10 amino acid residues: VFAFAMAFML (amidated-C-terminus amino acid) mimicking the interacting domain of CaM with Aβ (1–42), using a combined strategy based on the experimental results obtained for Aβ(1–42) binding to CaM and in silico docking analysis. The increase in the fluorescence intensity of Aβ(1–42) HiLyteTM-Fluor555 has been used to monitor the kinetics of complex formation with CaM and with calbindin-D28k. The complexation between nanomolar concentrations of Aβ(1–42) and calbindin-D28k is also a novel finding reported in this work. We found that the synthetic peptide VFAFAMAFML (amidated-C-terminus amino acid) is a potent inhibitor of the formation of Aβ(1–42):CaM and of Aβ(1–42):calbindin-D28k complexes.

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Section: Expression and Purification Of Calbindin-d28kmentioning

confidence: 99%

Design and Experimental Evaluation of a Peptide Antagonist against Amyloid β(1–42) Interactions with Calmodulin and Calbindin-D28k

Salazar

Poejo

Mata

et al. 2022

IJMS

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“…Several novel structures have been solved based on the long wavelength data collected at I23 over the past two years. [28][29][30][31][32][33] The first published structure was that of ThcOx, an oxidase protein from the cyanobactin pathway. 34 Fig.3c.…”

Section: ．Resultsmentioning

confidence: 99%

The Long-wavelength Macromolecular Crystallography I23 at Diamond Light Source

Wagner

Duman

Omari

et al. 2018

Journal of the Crystallographic Society of Japan

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“…There is evidence that modulation of IMPase away from the active site and dimer interface can affect activity; synthetic peptides that disrupt IMPase-calbindin interactions prevent calbindin-mediated activation of IMPase (Noble et al, 2018) and mediate antidepressant-like effects in mice (Levi et al, 2013). It is possible that ebselen interferes with accessory protein binding, possibly by formation of the tetramer seen in the crystal, to moderate the activity of IMPase in vivo.…”

Section: Discussionmentioning

confidence: 99%

Crystallization and structure of ebselen bound to Cys141 of human inositol monophosphatase

Fenn

Waller-Evans

Atack

et al. 2020

Acta Crystallogr F Struct Biol Commun

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Inositol monophosphatase (IMPase) is inhibited by lithium, which is the most efficacious treatment for bipolar disorder. Several therapies have been approved, or are going through clinical trials, aimed at the replacement of lithium in the treatment of bipolar disorder. One candidate small molecule is ebselen, a selenium-containing antioxidant, which has been demonstrated to produce lithium-like effects both in a murine model and in clinical trials. Here, the crystallization and the first structure of human IMPase covalently complexed with ebselen, a 1.47 Å resolution crystal structure (PDB entry 6zk0), are presented. In the complex with human IMPase, ebselen in a ring-opened conformation is covalently attached to Cys141, a residue located away from the active site. IMPase is a dimeric enzyme and in the crystal structure two adjacent dimers share four ebselen molecules, creating a tetramer with approximate 222 symmetry. In the crystal structure presented in this publication, the active site in the tetramer is still accessible, suggesting that ebselen may function as an allosteric inhibitor or may block the binding of partner proteins.

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The X-ray structure of human calbindin-D28K: an improved model

Abstract: The X-ray structure of human calbindin-D28K, a calcium-buffering protein that is highly expressed in the central nervous system, is reported.

Cited by 21 publications

References 47 publications

Design and Experimental Evaluation of a Peptide Antagonist against Amyloid β(1–42) Interactions with Calmodulin and Calbindin-D28k

Design and Experimental Evaluation of a Peptide Antagonist against Amyloid β(1–42) Interactions with Calmodulin and Calbindin-D28k

The Long-wavelength Macromolecular Crystallography I23 at Diamond Light Source

Crystallization and structure of ebselen bound to Cys141 of human inositol monophosphatase

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