Interaction of serum amyloid P component with hexanoyl bis(<scp>D</scp>-proline) (CPHPC)

Kolstoe, Simon; Jenvey, Michelle C.; Purvis, Alan; Light, Mark E.; Thompson, Darren A.; Hughes, P.I.; Pepys, Mark B.; Wood, Stephen P.

doi:10.1107/s1399004714013455

Cited by 15 publications

(11 citation statements)

References 33 publications

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“…We used atomic coordinates of serum amyloid P component (SAP) homo-pentamer (PDB entry: 4AVS) 32 . Two calcium ions bound to SAP subunits were retained in the atomic coordinates of this SAP system.…”

Section: Methodsmentioning

confidence: 99%

“…A ring opening of the SAP pentamer occurs in a relatively early stage of hcbMC/MD cycles (Table 2) and is followd by the initial steps of SAP pentamer disassembly process, that is, tetramer-monomer and trimer-dimer dissociation reactions (see Figure 3). 32 . A ring-opened SAP pentamer appearing in experimental conditions might be assigned into partially unfolded SAP pentamer in the context of mass spectroscopy.…”

Section: Free Energy Profile Of Ring-opening Reaction Of Sap Pentamermentioning

confidence: 99%

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Reaction Pathway Sampling and Free Energy Analyses for Multimeric Protein Complex Disassembly with Employing Hybrid Configuration Bias Monte Carlo/Molecular Dynamics Simulation

Kurisaki

Tanaka

2020

Preprint

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Physicochemical characterization of multimeric biomacromolecule assembly and disassembly processes is a milestone to understand the mechanisms for biological phenomena at molecular level. Mass spectroscopy (MS) and structural bioinformatics (SB) approaches have become feasible to identify subcomplexes involved in assembly and disassembly, while they cannot provide atomic information sufficient for free energy calculation to characterize transition mechanism between two different sets of subcomplexes. To combine observations derived from MS and SB approaches with conventional free energy calculation protocols, we here designed a new reaction pathway sampling method with employing hybrid configuration bias Monte Carlo/Molecular Dynamics (hcbMC/MD) scheme and applied it to simulate disassembly process of serum amyloid P component (SAP) pentamer. The results we obtained are consistent with those of the earlier MS and SB studies with respect to SAP subcomplex species and the initial stage of SAP disassembly processes. Furthermore, we observed a novel dissociation event, ring-opening reaction of SAP pentamer. Employing free energy calculation combined with the hcbMC/MD reaction pathway trajectories, we moreover obtained experimentally testable observations on (1) reaction time of the ring-opening reaction and (2) importance of Asp42 and Lys117 for stable formation of SAP oligomer.TOC graphics

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Section: Methodsmentioning

confidence: 99%

Section: Free Energy Profile Of Ring-opening Reaction Of Sap Pentamermentioning

confidence: 99%

Reaction Pathway Sampling and Free Energy Analyses for Multimeric Protein Complex Disassembly with Employing Hybrid Configuration Bias Monte Carlo/Molecular Dynamics Simulation

Kurisaki

Tanaka

2020

Preprint

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“…We built a 3D model of zebrafish CA VI starting from PDB 3FE4, human CA VI ( Pilka et al, 2012 ); and 4AVS, human SAP component ( Kolstoe et al, 2014 ), as templates for the CA domain and PTX domain, respectively. The CA template includes residues 32–280 of human CA VI, missing 14 residues in the N-terminus of the mature protein, and 28 residues in the C-terminus.…”

Section: Methodsmentioning

confidence: 99%

Identification and characterization of a novel zebrafish (Danio rerio) pentraxin–carbonic anhydrase

Patrikainen

Tolvanen

Aspatwar

et al. 2017

PeerJ

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BackgroundCarbonic anhydrases (CAs) are ubiquitous, essential enzymes which catalyze the conversion of carbon dioxide and water to bicarbonate and H+ ions. Vertebrate genomes generally contain gene loci for 15–21 different CA isoforms, three of which are enzymatically inactive. CA VI is the only secretory protein of the enzymatically active isoforms. We discovered that non-mammalian CA VI contains a C-terminal pentraxin (PTX) domain, a novel combination for both CAs and PTXs.MethodsWe isolated and sequenced zebrafish (Danio rerio) CA VI cDNA, complete with the sequence coding for the PTX domain, and produced the recombinant CA VI–PTX protein. Enzymatic activity and kinetic parameters were measured with a stopped-flow instrument. Mass spectrometry, analytical gel filtration and dynamic light scattering were used for biophysical characterization. Sequence analyses and Bayesian phylogenetics were used in generating hypotheses of protein structure and CA VI gene evolution. A CA VI–PTX antiserum was produced, and the expression of CA VI protein was studied by immunohistochemistry. A knock-down zebrafish model was constructed, and larvae were observed up to five days post-fertilization (dpf). The expression of ca6 mRNA was quantitated by qRT-PCR in different developmental times in morphant and wild-type larvae and in different adult fish tissues. Finally, the swimming behavior of the morphant fish was compared to that of wild-type fish.ResultsThe recombinant enzyme has a very high carbonate dehydratase activity. Sequencing confirms a 530-residue protein identical to one of the predicted proteins in the Ensembl database (ensembl.org). The protein is pentameric in solution, as studied by gel filtration and light scattering, presumably joined by the PTX domains. Mass spectrometry confirms the predicted signal peptide cleavage and disulfides, and N-glycosylation in two of the four observed glycosylation motifs. Molecular modeling of the pentamer is consistent with the modifications observed in mass spectrometry. Phylogenetics and sequence analyses provide a consistent hypothesis of the evolutionary history of domains associated with CA VI in mammals and non-mammals. Briefly, the evidence suggests that ancestral CA VI was a transmembrane protein, the exon coding for the cytoplasmic domain was replaced by one coding for PTX domain, and finally, in the therian lineage, the PTX-coding exon was lost. We knocked down CA VI expression in zebrafish embryos with antisense morpholino oligonucleotides, resulting in phenotype features of decreased buoyancy and swim bladder deflation in 4 dpf larvae.DiscussionThese findings provide novel insights into the evolution, structure, and function of this unique CA form.

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“…In fact, SAP knockout mice showed inhibited amyloid formation [86]. SAP was identified as a therapeutic target, which then led to development of CPHPC, a drug that inhibits the binding of SAP to amyloid deposits [87]. The activity of this agent relates to its ability to cross-link SAP molecule pairs face to face, which results in rapid hepatic clearance and completely blocks the binding face of the SAP molecule [88].…”

Section: Immunotherapy For Aa Amyloidosis Secondary To Ramentioning

confidence: 99%

Developments in the Treatment of Amyloid A Amyloidosis Secondary to Rheumatoid Arthritis

Nakamura¹

2016

Exploring New Findings on Amyloidosis

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Amyloidosis refers to a heterogeneous group of diseases in which a soluble precursor, misfolded protein, and subsequently aggregates into highly structured protein fibrils with a cross--pleated structure. Of these diseases, amyloid A AA amyloidosis is a complication of long-standing inflammatory diseases such as rheumatoid arthritis RA . Treatment of this amyloidosis with RA aims to stop serum AA protein production. Immunosuppressants have reportedly been useful for both RA inflammation and AA amyloidosis. Also, biologics are effective for these specific pathological processes by targeting key players in each inflammation. In addition to the above-mentioned medications, agents both inhibiting AA fibrillogenesis and destabilizing AA fibrils have recently been employed. Phagocytes play important roles in the regression of AA fibrils. Renal involvement is the most common complication in AA amyloidosis. Peritoneal dialysis, hemodialysis, and even renal transplantation are available for patients with end-stage renal disease and AA amyloidosis. This chapter thus discusses current developments in the treatment of AA amyloidosis secondary to RA.

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Interaction of serum amyloid P component with hexanoyl bis(D-proline) (CPHPC)

Cited by 15 publications

References 33 publications

Reaction Pathway Sampling and Free Energy Analyses for Multimeric Protein Complex Disassembly with Employing Hybrid Configuration Bias Monte Carlo/Molecular Dynamics Simulation

Reaction Pathway Sampling and Free Energy Analyses for Multimeric Protein Complex Disassembly with Employing Hybrid Configuration Bias Monte Carlo/Molecular Dynamics Simulation

Identification and characterization of a novel zebrafish (Danio rerio) pentraxin–carbonic anhydrase

Developments in the Treatment of Amyloid A Amyloidosis Secondary to Rheumatoid Arthritis

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