A structural model for across membrane coupling between the Qo and Qi active sites of cytochrome bc1

The geometries, vibrational frequencies, electronic properties and reactivity of potassium supported on SBA-15 have been theoretically investigated by the density functional theory (DFT) method. The structural model of the potassium supported on SBA-15 was constructed based on our previous work [Wang ZX, Wang DX, Zhao Z, Chen Y, Lan J, A DFT study of the structural units in SBA-15 mesoporous molecular sieve, Comput. Theor. Chem.963, 403, 2011]. This paper is the extension of our previous work. The most favored location of potassium atom was obtained by the calculation of substitution energy. The calculated vibrational frequencies of K /SBA-15 are in good agreement with the experimental results. By analyzing the properties of electronic structure, we found that the O atom of Si - O (2)- K group acts as the Lewis base center and the K atom acts as the Lewis acid center. The reactivity of K /SBA-15 was investigated by calculating the activation of oxygen molecule. The oxygen molecule can be activated by K /SBA-15 with an energy barrier of 103.2 kJ/mol. In the final state, the activated oxygen atoms become new Lewis acid centers, which are predicted to act as the active sites in the catalytic reactions. This study provides a deep insight into the properties of supported potassium catalysts and offers fundamental information for further research.

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Structural Modeling and Analysis of Pregnancy-Associated Glycoprotein-1 of Buffalo (Bubalus bubalis)

ISRN Molecular Biology ◽

10.5402/2012/481539 ◽

2012 ◽

Vol 2012 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Jerome Andonissamy ◽

S. K. Singh ◽

S. K. Agarwal

Keyword(s):

Protein Structure ◽

Active Sites ◽

Structural Model ◽

Protein Structures ◽

Structural Modeling ◽

Bubalus Bubalis ◽

High Energy ◽

Docking Studies ◽

Modeling And Analysis ◽

Structural Conformity

The present study was conducted to design and analyze the structural model of buffalo pregnancy-associated glycoprotein-1 (PAG-1) using bioinformatics. Structural modeling of the deduced buffalo PAG-1 protein was done using PHYRE, CONSURF servers and its structure was subsequently constructed using MODELLER 9.9 and PyMOL softwares Buffalo PAG-1 structural conformity was analyzed using PROSA, WHATIF, and 3D-PSSM servers. Designed buffalo PAG-1 protein structure on BLAST analysis retrieved protein structures belonging to aspartic proteinase family. Moreover in silico analysis revealed buffalo PAG-1 protein retained bilobed structure with pepstatin-binding clefts near the active sites by docking studies with pepstatin A using PatchDock server. Structural studies revealed that the amino and carboxy terminal containing aspartic residues are highly conserved and buried within the protein structure. Structural conformity studies showed that more than 90% of the residues lie inside favored and allowed regions. It was also deduced that buffalo PAG-1 possesses low and high energy zones with a very low threshold for proteolysis ascertaining the stableness of the buffalo PAG-1 protein structure. This study depicts the structural conformity and stability of buffalo PAG-1 protein.

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Towards an Atomic-Scale Understanding of the Adsorbate-Driven Formation of High-Index Faces

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.1094.168 ◽

2015 ◽

Vol 1094 ◽

pp. 168-173

Author(s):

Xiu E Ren ◽

Jian Hui Zhang ◽

Xiao Dan Lv ◽

Qi Dan Chen

Keyword(s):

Active Sites ◽

Structural Model ◽

Geometric Approach ◽

High Index ◽

Atomic Scale ◽

Metallic Ions ◽

Preferential Adsorption ◽

Symmetry Operators ◽

Induced Changes ◽

Kdp Crystals

Preferential adsorption takes place at the step ledge between adjacent crystal faces, which usually serve as active sites for breaking chemical bonds. In this paper, we present a structural model to interpret the habit modification of single crystals in terms of the step geometries relationship between crystal faces. A new series of high index faces parallel to the ledge between adjacent facets can be explicitly determined from the presence of the symmetry operators in the space group. The relative stability of these new faces undergoes a faceting transition, driven by the adsorbate-induced changes of the step configuration. Combined with the chemical bond-geometric approach, our predictions accurately reproduce the tapering evolutions of KDP crystals in the present of metallic ions. The current work provides a new insight on how changes affecting elementary steps on one face are translated into the emergence of a new crystallographic face.

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Metal insertion into the molybdenum cofactor: product–substrate channelling demonstrates the functional origin of domain fusion in gephyrin

Biochemical Journal ◽

10.1042/bj20121078 ◽

2013 ◽

Vol 450 (1) ◽

pp. 149-157 ◽

Cited By ~ 35

Author(s):

Abdel A. Belaidi ◽

Guenter Schwarz

Keyword(s):

Alternative Splicing ◽

Active Sites ◽

Structural Model ◽

Molybdenum Cofactor ◽

Protein Domain ◽

Inhibitory Synapses ◽

Dependent Manner ◽

Domain Fusion ◽

Metal Insertion ◽

Substrate Channelling

The complexity of eukaryotic multicellular organisms relies on evolutionary developments that include compartmentalization, alternative splicing, protein domain fusion and post-translational modification. Mammalian gephyrin uniquely exemplifies these processes by combining two enzymatic functions within the biosynthesis of the Moco (molybdenum cofactor) in a multidomain protein. It also undergoes extensive alternative splicing, especially in neurons, where it also functions as a scaffold protein at inhibitory synapses. Two out of three gephyrin domains are homologous to bacterial Moco-synthetic proteins (G and E domain) while being fused by a third gephyrin-specific central C domain. In the present paper, we have established the in vitro Moco synthesis using purified components and demonstrated an over 300-fold increase in Moco synthesis for gephyrin compared with the isolated G domain, which synthesizes adenylylated molybdopterin, and E domain, which catalyses the metal insertion at physiological molybdate concentrations in an ATP-dependent manner. We show that the C domain impacts the catalytic efficacy of gephyrin, suggesting an important structural role in product–substrate channelling as depicted by a structural model that is in line with a face-to-face orientation of both active sites. Our functional studies demonstrate the evolutionary advantage of domain fusion in metabolic proteins, which can lead to the development of novel functions in higher eukaryotes.

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Chemical IN04 Inhibits the Kinase Domain not the ROC Domain of LRRK1: Results from Homology Modeling and Molecular Docking

Medicinal Chemistry ◽

10.2174/1573406416666200924125620 ◽

2020 ◽

Vol 16 ◽

Author(s):

Zhenhang Chen ◽

Weirong Xing ◽

Li Fan

Keyword(s):

Bone Loss ◽

Active Site ◽

Active Sites ◽

Structural Model ◽

Osteoporotic Fractures ◽

Salt Bridge ◽

Homology Model ◽

The Elderly ◽

Kinase Domain ◽

Binding Modes

Background: Bone loss is the most common reason for broken bones among the elderly. An ideal agent for treatment of bone loss should have both osteoclast inhibitory and osteoblast stimulatory functions. Leucine rich repeat kinase 1 (LRRK1) is a novel target for alternative anti-resorptive drugs to treat osteoporosis and osteoporotic fractures. Recently a chemical IN04, Methyl 3-[(([5-(3,5-dimethoxyphenyl)-1,3,4-oxadiazol-2-yl]-thio-acetyl)-amino]-benzoate, has been identified as a potential LRRK1 inhibitor. Objective: The aim of this work is to investigate how the chemical IN04 interacts with LRRK1 and inhibits its activity. Methods: A structural model of LRRK1 kinase domain was constructed with SWISS-MODEL. The human protein kinase ROCO4 (PDB ID: 4YZN) was chosen as the template based on sequence homology, structural and phylogenetic analysis. In addition, a homology model of the LRRK1 ROC domain was also prepared based on the LRRK2 ROC domain structure (PDB ID: 2ZEJ). The interactions of IN04 with the active sites in the LRRK1 kinase domain and ROC domain were investigated by SwissDock. Results: IN04 was docked into the active site of the LRRK1 kinase domain with similar interactions as ATP comparable to the ligand bound to homologous kinases. Many rational binding modes of IN04 to LRRK1 kinase domain were investigated and the most likely binding pose containing multiple hydrogen bonds and a salt bridge was discovered. However, IN04 cannot fit into the GDP-binding site of the ROC domain. Conclusion: Chemical IN04 inhibits LRRK1 by binding to the active site of the kinase domain but not the ROC domain.

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Resonant active sites in catalytic ammonia synthesis: A structural model

Surface Science ◽

10.1016/j.susc.2015.10.042 ◽

2016 ◽

Vol 645 ◽

pp. 41-48 ◽

Cited By ~ 4

Author(s):

Alexander R. Cholach ◽

Anna A. Bryliakova ◽

Andrey V. Matveev ◽

Nikolai N. Bulgakov

Keyword(s):

Active Sites ◽

Structural Model ◽

Ammonia Synthesis ◽

Catalytic Ammonia Synthesis

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Supramolecular Stabilization of a Tris(imidazolyl) Zn−Aqua Complex Evidenced by X-ray Analysis: A Structural Model for Mono-Zinc Active Sites of Enzymes

Journal of the American Chemical Society ◽

10.1021/ja016345e ◽

2001 ◽

Vol 123 (34) ◽

pp. 8442-8443 ◽

Cited By ~ 53

Author(s):

Olivier Sénèque ◽

Marie-Noëlle Rager ◽

Michel Giorgi ◽

Olivia Reinaud

Keyword(s):

Active Sites ◽

Structural Model ◽

Aqua Complex ◽

X Ray

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Inhibitory Proteins Block Substrate Access to the Active Site of Bacillus subtilis Intramembrane Metalloprotease SpoIVFB

10.1101/2021.07.09.451828 ◽

2021 ◽

Author(s):

Sandra Olenic ◽

Lim Heo ◽

Michael Feig ◽

Lee Kroos

Keyword(s):

Bacillus Subtilis ◽

Active Site ◽

Active Sites ◽

Structural Model ◽

Terminal Region ◽

Cross Linking ◽

Intramembrane Proteases ◽

Inhibitory Proteins ◽

Partial Homology ◽

Active Site Region

Intramembrane proteases of diverse signaling pathways use membrane-embedded active sites to cleave membrane-associated substrates. Interactions of intramembrane metalloproteases with modulators are poorly understood. Inhibition of Bacillus subtilis intramembrane metalloprotease SpoIVFB requires BofA and SpoIVFA, which transiently prevent cleavage of Pro-σK during endosporulation. Three conserved BofA residues (N48, N61, T64) in or near predicted transmembrane segment (TMS) 2 were found to be required for SpoIVFB inhibition. Disulfide cross-linking indicated that BofA TMS2 occupies the SpoIVFB active site region. BofA and SpoIVFA neither prevented SpoIVFB from interacting with Pro-σK in co-purification assays nor interfered with cross-linking between the C-terminal regions of Pro-σK and SpoIVFB. However, BofA and SpoIVFA did interfere with cross-linking between the N-terminal Proregion of Pro-σK and the SpoIVFB active site region and interdomain linker. A BofA variant lacking predicted TMS1, in combination with SpoIVFA, was less effective at interfering with some of the cross-links and slightly less effective at inhibiting cleavage of Pro-σK by SpoIVFB. A structural model was built of SpoIVFB in complex with BofA and parts of SpoIVFA and Pro-σK, using partial homology and constraints from cross-linking and co-evolutionary analyses. The model predicts that N48 in BofA TMS2 interacts with T64 (and possibly N61) of BofA to stabilize a membrane-embedded C-terminal region. SpoIVFA is predicted to bridge the BofA C-terminal region and SpoIVFB. Thus, the two inhibitory proteins block access of the Pro-σK N-terminal region to the SpoIVFB active site region. Our findings may inform efforts to develop selective inhibitors of intramembrane metalloproteases.

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