Three-Dimensional Architecture of the L-Type Calcium Channel: Structural Insights into the CaVα2δ1 Auxiliary Protein

In most of the pathogenic organisms including Plasmodium falciparum, isoprenoids are synthesized via MEP (MethylErythritol 4-Phosphate) pathway. LytB is the last enzyme of this pathway which catalyzes the conversion of (E)-4-hydroxy-3-methylbut-2-en-1-yl diphosphate (HMBPP) into the two isoprenoid precursors: isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). Since the MEP pathway is not used by humans, it represents an attractive target for the development of new antimalarial compounds or inhibitors. Here a systematic in-silico study has been conducted to get an insight into the structure of Plasmodium lytB as well as its affinities towards different inhibitors. We used comparative modeling technique to predict the three dimensional (3D) structure of Plasmodium LytB taking E. Coli LytB protein (PDB ID: 3KE8) as template and the model was subsequently refined through molecular dynamics (MD) simulation. A large ligand dataset containing diphospate group was subjected for virtual screening against the target using GOLD 5.2 program. Considering the mode of binding and affinities, 17 leads were selected on basis of binding energies in comparison to its substrate HMBPP (Gold.Chemscore.DG: -20.9734 kcal/mol). Among them, 5 were discarded because of their inhibitory activity towards other human enzymes. The rest 12 potential leads carry all the properties of any "drug like" molecule and the knowledge of Plasmodium LytB inhibitory mechanism which can provide valuable support for the antimalarial inhibitor design in future.

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Three-Dimensional Finite Element Model to Study Effect of RyR Calcium Channel, ER Leak and SERCA Pump on Calcium Distribution in Oocyte Cell

International Journal of Computational Methods ◽

10.1142/s0219876218500913 ◽

2018 ◽

Vol 16 (01) ◽

pp. 1850091 ◽

Cited By ~ 4

Author(s):

Parvaiz Ahmad Naik ◽

Kamal Raj Pardasani

Keyword(s):

Finite Element ◽

Calcium Channel ◽

Concentration Distribution ◽

Calcium Concentration ◽

Three Dimensional ◽

Element Model ◽

Dimensional Finite Element ◽

Serca Pump ◽

Spatio Temporal ◽

Three Dimensional Finite Element

Calcium ions control many cellular processes by relaying signals in the form of their spatio-temporal distribution. Dynamics and patterns of calcium concentration such as repetitive waves, coherent oscillations or spatially localized elevations activate diverse physiological functions. Calcium is the most universal second messenger in cells and plays an important role in initiation, sustenance and termination of various activities in cells required for maintaining the structure and function of the cell. Calcium signal at fertilization is necessary for egg activation and exhibits specialized spatial and temporal dynamics. The specific calcium concentration distribution patterns in oocytes required for various activities like egg fertilization, maturation, etc. are not well understood. In this paper, a three-dimensional finite element model is proposed to study the spatio-temporal calcium distribution in oocytes. The parameters such as buffers, SERCA pump, ER Leak, ryanodine receptor (RyR) calcium channel, point source and line source of calcium are incorporated in the model. The appropriate initial and boundary conditions have been framed on the basis of the physical condition of the problem. A program is developed in MATLAB for simulation. The results have been used to study the effect of source geometry, RyR calcium channel, ER Leak, SERCA pump and buffers on cytosolic calcium concentration distribution in oocytes.

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Three-dimensional structure of calcium channel activater Imperatoxin A determined by NMR specroscopy.

Seibutsu Butsuri ◽

10.2142/biophys.39.s104_3 ◽

1999 ◽

Vol 39 (supplement) ◽

pp. S104

Author(s):

K. Takeuchi ◽

J. I. Kim ◽

H. Takahashi ◽

K. Sato ◽

I. Shimada

Keyword(s):

Calcium Channel ◽

Three Dimensional ◽

Dimensional Structure ◽

Three Dimensional Structure

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NMR and Restrained Molecular Dynamics Study of the Three-Dimensional Solution Structure of Toxin FS2, a Specific Blocker of the L-Type Calcium Channel, Isolated from Black Mamba Venom

Biochemistry ◽

10.1021/bi00017a022 ◽

1995 ◽

Vol 34 (17) ◽

pp. 5923-5937 ◽

Cited By ~ 39

Author(s):

Jean-Pierre Albrand ◽

Martin J. Blackledge ◽

Franck Pascaud ◽

Michelle Hollecker ◽

Dominique Marion

Keyword(s):

Molecular Dynamics ◽

Calcium Channel ◽

Solution Structure ◽

Three Dimensional ◽

Dimensional Solution ◽

Restrained Molecular Dynamics

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Structural insights into vesicle amine transport-1 (VAT-1) as a member of the NADPH-dependent quinone oxidoreductase family

Scientific Reports ◽

10.1038/s41598-021-81409-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Sun-Yong Kim ◽

Tomoyuki Mori ◽

Min Fey Chek ◽

Shunji Furuya ◽

Ken Matsumoto ◽

...

Keyword(s):

Three Dimensional ◽

Bound State ◽

Dimensional Structure ◽

Molecular Function ◽

Quinone Oxidoreductase ◽

Oxidoreductase Activity ◽

Putative Active Site ◽

Binding Cleft ◽

Phospholipid Transport ◽

Structural Insights

AbstractVesicle amine transport protein-1 (VAT-1) has been implicated in the regulation of vesicular transport, mitochondrial fusion, phospholipid transport and cell migration, and is a potential target of anticancer drugs. Little is known about the molecular function of VAT-1. The amino acid sequence indicates that VAT-1 belongs to the quinone oxidoreductase subfamily, suggesting that VAT-1 may possess enzymatic activity in unknown redox processes. To clarify the molecular function of VAT-1, we determined the three-dimensional structure of human VAT-1 in the free state at 2.3 Å resolution and found that VAT-1 forms a dimer with the conserved NADPH-binding cleft on each protomer. We also determined the structure of VAT-1 in the NADP-bound state at 2.6 Å resolution and found that NADP binds the binding cleft to create a putative active site with the nicotine ring. Substrate screening suggested that VAT-1 possesses oxidoreductase activity against quinones such as 1,2-naphthoquinone and 9,10-phenanthrenequinone.

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Comparison of three-dimensional solution structures of dendrotoxin I, a potassium channel blocker, and calucicludine, a calcium channel blocker, determined by nuclear magnetic resonance spectroscopy

Peptide Science — Present and Future ◽

10.1007/0-306-46864-6_106 ◽

2006 ◽

pp. 311-312

Author(s):

E. Katoh ◽

H. Nishio ◽

T. Inui ◽

Y. Nishiuchi ◽

T. Kimura ◽

...

Keyword(s):

Nuclear Magnetic Resonance ◽

Magnetic Resonance ◽

Magnetic Resonance Spectroscopy ◽

Potassium Channel ◽

Calcium Channel ◽

Channel Blocker ◽

Three Dimensional ◽

Resonance Spectroscopy ◽

Dimensional Solution ◽

Solution Structures

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Three-Dimensional Structure of AAA ATPase Vps4: Advancing Structural Insights into the Mechanisms of Endosomal Sorting and Enveloped Virus Budding

Structure ◽

10.1016/j.str.2008.12.020 ◽

2009 ◽

Vol 17 (3) ◽

pp. 427-437 ◽

Cited By ~ 40

Author(s):

Michael John Landsberg ◽

Parimala Rao Vajjhala ◽

Rosalba Rothnagel ◽

Alan Leslie Munn ◽

Ben Hankamer

Keyword(s):

Three Dimensional ◽

Dimensional Structure ◽

Virus Budding ◽

Three Dimensional Structure ◽

Endosomal Sorting ◽

Aaa Atpase ◽

Enveloped Virus ◽

Structural Insights

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Structural Insights of Supported Nanoparticles By Z-Contrast and High Resolution Electron Microscopy

Microscopy and Microanalysis ◽

10.1017/s1431927600031585 ◽

2001 ◽

Vol 7 (S2) ◽

pp. 1102-1103

Author(s):

Judith C. Yang ◽

Erin Devlin ◽

William Rhodes ◽

Steven Bradley

Keyword(s):

Electron Microscopy ◽

Three Dimensional ◽

High Resolution Electron Microscopy ◽

Dark Field ◽

Contrast Imaging ◽

Essential Information ◽

Support Materials ◽

Annular Dark Field ◽

Z Contrast ◽

Structural Insights

A vital component to nanoparticle science will be the three dimensional (3-D) characterization of both structure and chemistry of these nanoparticles on their supports at the nanometer scale and below. to achieve this goal, quantitative Z-contrast and atomic resolution will provide essential information about their structure. Z-contrast imaging is ideal for imaging these large Z nanoparticles on low Z supports. in this proceedings, we present a quantitative Z-contrast method to determine number of atoms and a few examples of a combination of electron microscopy methods to gain structural insights into supported nanoparticle, such as Pt on different support materials, PtRu5 on C and Pt-Sn on SiO2.A relatively new and powerful method is to determine the number of atoms in a nanoparticle, by very high angle annular dark-field (HAADF) imaging or Z-contrast technique [1, 2]. We have shown that quantification of the absolute image intensity from very HAADF microscopy will provide the number of atoms in very small particles of high atomic number to ±2 atoms for Re6 nanoparticles supported on carbon [3].

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