scholarly journals Crystal Structures of Apo and Metal-Bound Forms of the UreE Protein fromHelicobacter pylori: Role of Multiple Metal Binding Sites,

Biochemistry ◽  
2010 ◽  
Vol 49 (33) ◽  
pp. 7080-7088 ◽  
Author(s):  
Rong Shi ◽  
Christine Munger ◽  
Abdalin Asinas ◽  
Stéphane L. Benoit ◽  
Erica Miller ◽  
...  
Keyword(s):  
Crystal Structures ◽  
Metal Binding ◽  
Binding Sites ◽  
Metal Binding Sites

scholarly journals Molecular dynamics simulations of zfP2X4 receptors

2021 ◽  
Author(s):  
kalyan immadisetty ◽  
Peter Kekenes-Huskey
Keyword(s):  
Molecular Dynamics ◽  
Crystal Structures ◽  
Metal Binding ◽  
Binding Sites ◽  
Molecular Mechanisms ◽  
Pain Perception ◽  
Gulf Coast ◽  
Md Simulations ◽  
P2x Receptor ◽  
Metal Binding Sites

The ATP activated P2X4 receptor plays a prominent role in pain perception and modulation and thus may constitute an alternative therapeutic target for controlling pain. Given the biomedical relevance of P2X4 receptors, and poor understanding of molecular mechanisms that describe its gating by ATP, a fundamental understanding of the functional mechanism of these channels is warranted. Through classical all-atom molecular dynamics (MD) simulations we investigated the number of ATP molecules required to open (activate) the receptor for it to conduct ions. Since crystal structures of human P2X4 are not yet available, the crystal structures of highly-homologous zebrafish P2X4 (zfP2X4) structures were utilized for this study. It has been identified that at least two ATP molecules are required to prevent the open state receptor from collapsing back to a closed state. Additionally, we have discovered two metal binding sites, one at the intersection of the three monomers in the ectodomain (MBS1) and the second one near the ATP binding site (MBS2), both of which are occupied by the potassium ions. This observation draws its comparison to the gulf coast P2X receptor that it possesses the same two metal binding sites, however, MBS1 and MBS2 in this receptor are occupied by zinc and magnesium, respectively.

scholarly journals Intracellular trafficking of the human Wilson protein: the role of the six N-terminal metal-binding sites

2004 ◽  
Vol 380 (3) ◽  
pp. 805-813 ◽  
Author(s):  
Michael A. CATER ◽  
John FORBES ◽  
Sharon La FONTAINE ◽  
Diane COX ◽  
Julian F. B. MERCER
Keyword(s):  
Metal Binding ◽  
Binding Sites ◽  
Intracellular Trafficking ◽  
Copper Toxicity ◽  
Site Directed Mutagenesis ◽  
Metal Binding Sites ◽  
Wilson Protein ◽  
Necessary And Sufficient ◽  
Golgi Network

The Wilson protein (ATP7B) is a copper-transporting CPx-type ATPase defective in the copper toxicity disorder Wilson disease. In hepatocytes, ATP7B delivers copper to apo-ceruloplasmin and mediates the excretion of excess copper into bile. These distinct functions require the protein to localize at two different subcellular compartments. At the trans-Golgi network, ATP7B transports copper for incorporation into apo-ceruloplasmin. When intracellular copper levels are increased, ATP7B traffics to post-Golgi vesicles in close proximity to the canalicular membrane to facilitate biliary copper excretion. In the present study, we investigated the role of the six N-terminal MBSs (metal-binding sites) in the trafficking process. Using site-directed mutagenesis, we mutated or deleted various combinations of the MBSs and assessed the effect of these changes on the localization and trafficking of ATP7B. Results show that the MBSs required for trafficking are the same as those previously found essential for the copper transport function. Either MBS 5 or MBS 6 alone was sufficient to support the redistribution of ATP7B to vesicular compartments. The first three N-terminal motifs were not required for copper-dependent intracellular trafficking and could not functionally replace sites 4–6 when placed in the same sequence position. Furthermore, the N-terminal region encompassing MBSs 1–5 (amino acids 64–540) was not essential for trafficking, with only one MBS close to the membrane channel, necessary and sufficient to support trafficking. Our findings were similar to those obtained for the closely related ATP7A protein, suggesting similar mechanisms for trafficking between copper-transporting CPx-type ATPases.

scholarly journals The Role of GMXCXXC Metal Binding Sites in the Copper-induced Redistribution of the Menkes Protein

1999 ◽  
Vol 274 (16) ◽  
pp. 11170-11177 ◽  
Author(s):  
Daniel Strausak ◽  
Sharon La Fontaine ◽  
Joanne Hill ◽  
Stephen D. Firth ◽  
Paul J. Lockhart ◽  
...  
Keyword(s):  
Metal Binding ◽  
Binding Sites ◽  
Metal Binding Sites ◽  
Menkes Protein

scholarly journals BioMetAll: Identifying Metal-Binding Sites in Proteins from Backbone Preorganization

2020 ◽  
Author(s):  
José-Emilio Sánchez-Aparicio ◽  
Laura Tiessler-Sala ◽  
Lorea Velasco-Carneros ◽  
Lorena Roldán-Martín ◽  
Giuseppe Sciortino ◽  
...  
Keyword(s):  
Metal Binding ◽  
Binding Sites ◽  
De Novo ◽  
Conformational Transition ◽  
Protein Backbone ◽  
Metal Binding Sites ◽  
Structural Match ◽  
Geometric Descriptors ◽  
Metal Migration

<div><div><div><p>With a large amount of research dedicated to decoding how metallic species bind to protein, in silico methods are interesting allies for experimental procedures. To date, computational predictors mostly work by identifying the best possible sequence or structural match of the target protein with metal binding templates. These approaches are fundamentally focused on the first coordination sphere of the metal. Here, we present the BioMetAll predictor that is based on a different postulate: the formation of a potential metal-binding site is related to the geometric organization of the protein backbone. We first report the set of convenient geometric descriptors of the backbone needed for the algorithm and their parametrization from a statistical analysis. Then, the successful benchmark of BioMetAll on a set of more than 50 metal-binding X-Ray structures is presented. Because BioMetAll allows structural predictions regardless of the exact geometry of the side chains, it appears extremely valuable for systems which structures (either experimental or theoretical) are not optimal for metal binding sites. We report here its application on three different challenging cases i) the modulation of metal-binding sites during conformational transition in human serum albumin, ii) the identification of possible routes of metal migration in hemocyanins, and iii) the prediction of mutations to generate convenient metal-binding sites for de novo biocatalysts. This study shows that BioMetAll offers a versatile platform for numerous fields of research at the interface between inorganic chemistry and biology, and allows to highlight the role of the preorganization of the protein backbone as a marker for metal binding.</p></div></div></div>

scholarly journals BioMetAll: Identifying Metal-Binding Sites in Proteins from Backbone Preorganization

2020 ◽  
Author(s):  
José-Emilio Sánchez-Aparicio ◽  
Laura Tiessler-Sala ◽  
Lorea Velasco-Carneros ◽  
Lorena Roldán-Martín ◽  
Giuseppe Sciortino ◽  
...  
Keyword(s):  
Metal Binding ◽  
Binding Sites ◽  
De Novo ◽  
Conformational Transition ◽  
Protein Backbone ◽  
Metal Binding Sites ◽  
Structural Match ◽  
Geometric Descriptors ◽  
Metal Migration

<div><div><div><p>With a large amount of research dedicated to decoding how metallic species bind to protein, in silico methods are interesting allies for experimental procedures. To date, computational predictors mostly work by identifying the best possible sequence or structural match of the target protein with metal binding templates. These approaches are fundamentally focused on the first coordination sphere of the metal. Here, we present the BioMetAll predictor that is based on a different postulate: the formation of a potential metal-binding site is related to the geometric organization of the protein backbone. We first report the set of convenient geometric descriptors of the backbone needed for the algorithm and their parametrization from a statistical analysis. Then, the successful benchmark of BioMetAll on a set of more than 50 metal-binding X-Ray structures is presented. Because BioMetAll allows structural predictions regardless of the exact geometry of the side chains, it appears extremely valuable for systems which structures (either experimental or theoretical) are not optimal for metal binding sites. We report here its application on three different challenging cases i) the modulation of metal-binding sites during conformational transition in human serum albumin, ii) the identification of possible routes of metal migration in hemocyanins, and iii) the prediction of mutations to generate convenient metal-binding sites for de novo biocatalysts. This study shows that BioMetAll offers a versatile platform for numerous fields of research at the interface between inorganic chemistry and biology, and allows to highlight the role of the preorganization of the protein backbone as a marker for metal binding.</p></div></div></div>

The structure of a deoxygenated 400 kDa haemoglobin reveals ternary- and quaternary-structural changes of giant haemoglobins

2014 ◽  
Vol 70 (7) ◽  
pp. 1823-1831 ◽  
Author(s):  
Nobutaka Numoto ◽  
Taro Nakagawa ◽  
Ryota Ohara ◽  
Tomoyo Hasegawa ◽  
Akiko Kita ◽  
...  
Keyword(s):  
Crystal Structures ◽  
Metal Binding ◽  
Binding Sites ◽  
Structural Changes ◽  
Divalent Cations ◽  
Glycosylation Site ◽  
Metal Binding Sites ◽  
Molecular Masses ◽  
Quaternary Structures ◽  
Intersubunit Interactions

The quaternary structures of invertebrate haemoglobins (Hbs) are quite different from those of vertebrate Hbs. The extracellular giant Hbs of molecular masses of about 400 and 3600 kDa are composed of a dome-shaped dodecameric subassembly which consists of four individual globin subunits. Several crystal structures of 400 kDa Hbs from annelids have been reported, including structures in oxygenated and partially unliganded states, but the structure of the fully deoxygenated state has not been reported. In the present study, crystal structures of V2Hb from the tube wormLamellibrachia satsumahave been determined in both the fully oxygenated and deoxygenated states. A glycosylation site and novel metal-binding sites for divalent cations were clearly observed with no intersubunit interactions in V2Hb. A comparison of the oxygenated and the deoxygenated forms of V2Hb reveals that the ternary- and quaternary-structural changes occur in a manner that maintains the molecularD3symmetry. These structures suggest that the mechanisms of quaternary-structural changes between the oxy and deoxy states for the giant Hbs are identical across species.

scholarly journals Rational design of metal-binding sites in domain-swapped myoglobin dimers

2021 ◽  
Vol 217 ◽  
pp. 111374
Author(s):  
Satoshi Nagao ◽  
Ayaka Idomoto ◽  
Naoki Shibata ◽  
Yoshiki Higuchi ◽  
Shun Hirota
Keyword(s):  
Metal Binding ◽  
Binding Sites ◽  
Rational Design ◽  
Metal Binding Sites

scholarly journals Electron transfer pathways in photoexcited lanthanide(III) complexes of picolinate ligands

2021 ◽  
Author(s):  
Daniel Kovacs ◽  
Daniel Kocsi ◽  
Jordann A. L. Wells ◽  
Salauat R. Kiraev ◽  
Eszter Borbas
Keyword(s):  
Electron Transfer ◽  
Metal Binding ◽  
Binding Sites ◽  
Secondary Amide ◽  
Metal Binding Sites ◽  
Electron Transfer Pathways

A series of luminescent lanthanide(III) complexes consisting of 1,4,7-triazacyclononane frameworks and three secondary amide-linked carbostyril antennae were synthesised. The metal binding sites were augmented with two pyridylcarboxylate donors yielding octadentate...

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