Crystal Structure of a Glutamate/Aspartate Binding Protein Complexed with a Glutamate Molecule: Structural Basis of Ligand Specificity at Atomic Resolution

2008 ◽  
Vol 382 (1) ◽  
pp. 99-111 ◽  
Author(s):  
Yonglin Hu ◽  
Cheng-Peng Fan ◽  
Guangsen Fu ◽  
Deyu Zhu ◽  
Qi Jin ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Binding Protein ◽  
Atomic Resolution ◽  
Structural Basis ◽  
Ligand Specificity

scholarly journals Structural basis of the zinc-induced cytoplasmic aggregation of the RNA-binding protein SFPQ

2020 ◽  
Vol 48 (6) ◽  
pp. 3356-3365 ◽  
Author(s):  
Jie Huang ◽  
Mitchell Ringuet ◽  
Andrew E Whitten ◽  
Sofia Caria ◽  
Yee Wa Lim ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Cortical Neurons ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Zinc Binding ◽  
Structural Basis ◽  
Rna Biogenesis ◽  
Cytoplasmic Accumulation ◽  
Nucleocytoplasmic Distribution

Abstract SFPQ is a ubiquitous nuclear RNA-binding protein implicated in many aspects of RNA biogenesis. Importantly, nuclear depletion and cytoplasmic accumulation of SFPQ has been linked to neuropathological conditions such as Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS). Here, we describe a molecular mechanism by which SFPQ is mislocalized to the cytoplasm. We report an unexpected discovery of the infinite polymerization of SFPQ that is induced by zinc binding to the protein. The crystal structure of human SFPQ in complex with zinc at 1.94 Å resolution reveals intermolecular interactions between SFPQ molecules that are mediated by zinc. As anticipated from the crystal structure, the application of zinc to primary cortical neurons induced the cytoplasmic accumulation and aggregation of SFPQ. Mutagenesis of the three zinc-coordinating histidine residues resulted in a significant reduction in the zinc-binding affinity of SFPQ in solution and the zinc-induced cytoplasmic aggregation of SFPQ in cultured neurons. Taken together, we propose that dysregulation of zinc availability and/or localization in neuronal cells may represent a mechanism for the imbalance in the nucleocytoplasmic distribution of SFPQ, which is an emerging hallmark of neurodegenerative diseases including AD and ALS.

scholarly journals Structural basis of terephthalate recognition by solute binding protein TphC

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Trishnamoni Gautom ◽  
Dharmendra Dheeman ◽  
Colin Levy ◽  
Thomas Butterfield ◽  
Guadalupe Alvarez Gonzalez ◽  
...  
Keyword(s):  
Genetic Resource ◽  
Binding Protein ◽  
Structural Basis ◽  
Bacterial Cells ◽  
Ligand Specificity ◽  
Biological Degradation ◽  
Genomic Context ◽  
Context Analysis ◽  
Structural Characterisation ◽  
Genomic Context Analysis

AbstractBiological degradation of Polyethylene terephthalate (PET) plastic and assimilation of the corresponding monomers ethylene glycol and terephthalate (TPA) into central metabolism offers an attractive route for bio-based molecular recycling and bioremediation applications. A key step is the cellular uptake of the non-permeable TPA into bacterial cells which has been shown to be dependent upon the presence of the key tphC gene. However, little is known from a biochemical and structural perspective about the encoded solute binding protein, TphC. Here, we report the biochemical and structural characterisation of TphC in both open and TPA-bound closed conformations. This analysis demonstrates the narrow ligand specificity of TphC towards aromatic para-substituted dicarboxylates, such as TPA and closely related analogues. Further phylogenetic and genomic context analysis of the tph genes reveals homologous operons as a genetic resource for future biotechnological and metabolic engineering efforts towards circular plastic bio-economy solutions.

scholarly journals A Complexed Crystal Structure of a Single-Stranded DNA-Binding Protein with Quercetin and the Structural Basis of Flavonol Inhibition Specificity

2022 ◽  
Vol 23 (2) ◽  
pp. 588
Author(s):  
En-Shyh Lin ◽  
Ren-Hong Luo ◽  
Cheng-Yang Huang
Keyword(s):  
Crystal Structure ◽  
Binding Protein ◽  
Binding Activity ◽  
Structural Basis ◽  
Molecular Evidence ◽  
Mobility Shift ◽  
Single Stranded Dna ◽  
Ssdna Binding ◽  
Replacement Method ◽  
Ssdna Binding Protein

Single-stranded DNA (ssDNA)-binding protein (SSB) plays a crucial role in DNA replication, repair, and recombination as well as replication fork restarts. SSB is essential for cell survival and, thus, is an attractive target for potential antipathogen chemotherapy. Whether naturally occurring products can inhibit SSB remains unknown. In this study, the effect of the flavonols myricetin, quercetin, kaempferol, and galangin on the inhibition of Pseudomonas aeruginosa SSB (PaSSB) was investigated. Furthermore, SSB was identified as a novel quercetin-binding protein. Through an electrophoretic mobility shift analysis, myricetin could inhibit the ssDNA binding activity of PaSSB with an IC50 of 2.8 ± 0.4 μM. The effect of quercetin, kaempferol, and galangin was insignificant. To elucidate the flavonol inhibition specificity, the crystal structure of PaSSB complexed with the non-inhibitor quercetin was solved using the molecular replacement method at a resolution of 2.3 Å (PDB entry 7VUM) and compared with a structure with the inhibitor myricetin (PDB entry 5YUN). Although myricetin and quercetin bound PaSSB at a similar site, their binding poses were different. Compared with myricetin, the aromatic ring of quercetin shifted by a distance of 4.9 Å and an angle of 31o for hydrogen bonding to the side chain of Asn108 in PaSSB. In addition, myricetin occupied and interacted with the ssDNA binding sites Lys7 and Glu80 in PaSSB whereas quercetin did not. This result might explain why myricetin could, but quercetin could not, strongly inhibit PaSSB. This molecular evidence reveals the flavonol inhibition specificity and also extends the interactomes of the natural anticancer products myricetin and quercetin to include the OB-fold protein SSB.

scholarly journals Structural Basis of Chemokine Sequestration by a Tick Chemokine Binding Protein: The Crystal Structure of the Complex between Evasin-1 and CCL3

PLoS ONE ◽  
2009 ◽  
Vol 4 (12) ◽  
pp. e8514 ◽  
Author(s):  
João M. Dias ◽  
Christophe Losberger ◽  
Maud Déruaz ◽  
Christine A. Power ◽  
Amanda E. I. Proudfoot ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Binding Protein ◽  
Structural Basis

scholarly journals Structural basis of terephthalate recognition by solute binding protein TphC

2021 ◽  
Author(s):  
Trishna Gautom ◽  
Dharmendra Dheeman ◽  
Colin Levy ◽  
Thomas Butterfield ◽  
Lewis Caiger ◽  
...  
Keyword(s):  
Genetic Resource ◽  
Binding Protein ◽  
Structural Basis ◽  
Bacterial Cells ◽  
Ligand Specificity ◽  
Biological Degradation ◽  
Genomic Context ◽  
Context Analysis ◽  
Structural Characterisation ◽  
Genomic Context Analysis

Abstract Biological degradation of Polyethylene terephthalate (PET) plastic and assimilation of the corresponding monomers ethylene glycol and terephthalate (TPA) into central metabolism offers an attractive route for bio-based molecular recycling and bioremediation applications. A key step is the cellular uptake of the non-permeable TPA into bacterial cells which has been shown to be dependent upon the presence of the key tphC gene. However, little is known from a biochemical and structural perspective about the encoded solute binding protein, TphC. Here, we report the biochemical and structural characterisation of TphC in both open and TPA-bound closed conformations. This analysis demonstrates the narrow ligand specificity of TphC towards aromatic para-substituted dicarboxylates, such as TPA and closely related analogues. Further phylogenetic and genomic context analysis of the tph genes reveals homologous operons as a genetic resource for future biotechnological and metabolic engineering efforts towards circular plastic bio-economy solutions.

Sign in / Sign up

Export Citation Format

Share Document