scholarly journals Structural Adaptation of Cold-Active RTX Lipase fromPseudomonassp. Strain AMS8 Revealed via Homology and Molecular Dynamics Simulation Approaches

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Mohd. Shukuri Mohamad Ali ◽  
Siti Farhanie Mohd Fuzi ◽  
Menega Ganasen ◽  
Raja Noor Zaliha Raja Abdul Rahman ◽  
Mahiran Basri ◽  
...  
Keyword(s):  
Catalytic Domain ◽  
Industrial Applications ◽  
Structure And Function ◽  
Molecular Engineering ◽  
Dynamics Simulation ◽  
Structural Adaptation ◽  
C Terminus ◽  
Different Temperatures ◽  
And Function ◽  
3D Molecular Structure

The psychrophilic enzyme is an interesting subject to study due to its special ability to adapt to extreme temperatures, unlike typical enzymes. Utilizing computer-aided software, the predicted structure and function of the enzyme lipase AMS8 (LipAMS8) (isolated from the psychrophilicPseudomonassp., obtained from the Antarctic soil) are studied. The enzyme shows significant sequence similarities with lipases fromPseudomonassp. MIS38 andSerratia marcescens. These similarities aid in the prediction of the 3D molecular structure of the enzyme. In this study, 12 ns MD simulation is performed at different temperatures for structural flexibility and stability analysis. The results show that the enzyme is most stable at 0°C and 5°C. In terms of stability and flexibility, the catalytic domain (N-terminus) maintained its stability more than the noncatalytic domain (C-terminus), but the non-catalytic domain showed higher flexibility than the catalytic domain. The analysis of the structure and function of LipAMS8 provides new insights into the structural adaptation of this protein at low temperatures. The information obtained could be a useful tool for low temperature industrial applications and molecular engineering purposes, in the near future.

Structure prediction of SPAK C-terminal domain and analysis of its binding to RFXV/I motifs by homology modelling, docking, and molecular dynamics simulation studies

2020 ◽  
Vol 16 ◽  
Author(s):  
Mubarak A. Alamri ◽  
Ahmed D. Alafnan ◽  
Obaid Afzal ◽  
Alhumaidi B. Alabbas ◽  
Safar M. Alqahtani
Keyword(s):  
Molecular Dynamic ◽  
Dynamic Stability ◽  
Md Simulation ◽  
Homology Modelling ◽  
Antihypertensive Agents ◽  
Structure And Function ◽  
Dynamics Simulation ◽  
Dimensional Structure ◽  
Terminal Domain ◽  
And Function

Background: The STE20/SPS1-related proline/alanine-rich kinase (SPAK) is a component of WNKSPAK/OSR1 signaling pathway that plays an essential role in blood pressure regulation. The function of SPAK is mediated by its highly conserved C-terminal domain (CTD) that interacts with RFXV/I motifs of upstream activators, WNK kinases, and downstream substrate, cation-chloride cotransporters. Objective: To determine and validate the three-dimensional structure of the CTD of SPAK and to study and analyze its interaction with the RFXV/I motifs. Methods: A homology model of SPAK CTD was generated and validated through multiple approaches. The model was based on utilizing the OSR1 protein kinase as a template. This model was subjected to 100 ns molecular dynamic (MD) simulation to evaluate its dynamic stability. The final equilibrated model was used to dock the RFQV-peptide derived from WNK4 into the primary pocket that was determined based on the homology sequence between human SPAK and OSR1 CTDs. The mechanism of interaction, conformational rearrangement and dynamic stability of the binding of RFQV-peptide to SPAK CTD were characterized by molecular docking and molecular dynamic simulation. Results: The MD simulation suggested that the binding of RFQV induces a large conformational change due to the distribution of salt bridge within the loop regions. These results may help in understanding the relation between the structure and function of SPAK CTD and to support drug design of potential SPAK kinase inhibitors as antihypertensive agents. Conclusion: This study provides deep insight into SPAK CTD structure and function relationship.

Molecular Engineering of Conotoxins: The Importance of Loop Size to α-Conotoxin Structure and Function

2008 ◽  
Vol 51 (18) ◽  
pp. 5575-5584 ◽  
Author(s):  
Ai-Hua Jin ◽  
Norelle L. Daly ◽  
Simon T. Nevin ◽  
Ching-I A. Wang ◽  
Sebastien Dutertre ◽  
...  
Keyword(s):  
Structure And Function ◽  
Molecular Engineering ◽  
Loop Size ◽  
And Function

Structure and Function Relationship of Murine Insulin-like Peptide 5 (INSL5): Free C-Terminus Is Essential for RXFP4 Receptor Binding and Activation

Biochemistry ◽  
2011 ◽  
Vol 50 (39) ◽  
pp. 8352-8361 ◽  
Author(s):  
Alessia Belgi ◽  
Mohammed A. Hossain ◽  
Fazel Shabanpoor ◽  
Linda Chan ◽  
Suode Zhang ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Structure And Function ◽  
C Terminus ◽  
Function Relationship ◽  
Structure And Function Relationship ◽  
And Function ◽  
Relationship Of

Role of the C-Terminus of the High-Conductance Calcium-Activated Potassium Channel in Channel Structure and Function

Biochemistry ◽  
2005 ◽  
Vol 44 (30) ◽  
pp. 10135-10144 ◽  
Author(s):  
William A. Schmalhofer ◽  
Manuel Sanchez ◽  
Ge Dai ◽  
Ashvin Dewan ◽  
Lorena Secades ◽  
...  
Keyword(s):  
Potassium Channel ◽  
Structure And Function ◽  
Channel Structure ◽  
C Terminus ◽  
And Function ◽  
Calcium Activated Potassium Channel ◽  
High Conductance

scholarly journals Structure and Function of the Catalytic Domain of the Dihydrolipoyl Acetyltransferase Component inEscherichia coliPyruvate Dehydrogenase Complex

2014 ◽  
Vol 289 (22) ◽  
pp. 15215-15230 ◽  
Author(s):  
Junjie Wang ◽  
Natalia S. Nemeria ◽  
Krishnamoorthy Chandrasekhar ◽  
Sowmini Kumaran ◽  
Palaniappa Arjunan ◽  
...  
Keyword(s):  
Catalytic Domain ◽  
Structure And Function ◽  
Dihydrolipoyl Acetyltransferase ◽  
And Function ◽  
Dehydrogenase Complex

A urea channel from Bacillus cereus reveals a novel hexameric structure

2012 ◽  
Vol 445 (2) ◽  
pp. 157-166 ◽  
Author(s):  
Gerard H. M. Huysmans ◽  
Nathan Chan ◽  
Jocelyn M. Baldwin ◽  
Vincent L. G. Postis ◽  
Svetomir B. Tzokov ◽  
...  
Keyword(s):  
Bacillus Cereus ◽  
Structure And Function ◽  
Size Exclusion ◽  
Fluorescent Labelling ◽  
Transmembrane Helices ◽  
Cryo Electron Microscopy ◽  
C Terminus ◽  
Exclusion Chromatography ◽  
Urea Channel ◽  
And Function

Urea is exploited as a nitrogen source by bacteria, and its breakdown products, ammonia and bicarbonate, are employed to counteract stomach acidity in pathogens such as Helicobacter pylori. Uptake in the latter is mediated by UreI, a UAC (urea amide channel) family member. In the present paper, we describe the structure and function of UACBc, a homologue from Bacillus cereus. The purified channel was found to be permeable not only to urea, but also to other small amides. CD and IR spectroscopy revealed a structure comprising mainly α-helices, oriented approximately perpendicular to the membrane. Consistent with this finding, site-directed fluorescent labelling indicated the presence of seven TM (transmembrane) helices, with a cytoplasmic C-terminus. In detergent, UACBc exists largely as a hexamer, as demonstrated by both cross-linking and size-exclusion chromatography. A 9 Å (1 Å=0.1 nm) resolution projection map obtained by cryo-electron microscopy of two-dimensional crystals shows that the six protomers are arranged in a planar hexameric ring. Each exhibits six density features attributable to TM helices, surrounding a putative central channel, while an additional helix is peripherally located. Bioinformatic analyses allowed individual TM regions to be tentatively assigned to the density features, with the resultant model enabling identification of residues likely to contribute to channel function.

scholarly journals Inhibition of Mycobacterium-RmlA by Molecular Modeling, Dynamics Simulation, and Docking

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
N. Harathi ◽  
Madhusudana Pulaganti ◽  
C. M. Anuradha ◽  
Suresh Kumar Chitta
Keyword(s):  
Drug Targets ◽  
Rational Design ◽  
3D Structure ◽  
Reliability Assessment ◽  
Comparative Modeling ◽  
Structure And Function ◽  
Dynamics Simulation ◽  
Structural Refinement ◽  
And Function ◽  
Key Residues

The increasing resistance to anti-tb drugs has enforced strategies for finding new drug targets against Mycobacterium tuberculosis (Mtb). In recent years enzymes associated with the rhamnose pathway in Mtb have attracted attention as drug targets. The present work is on α-D-glucose-1-phosphate thymidylyltransferase (RmlA), the first enzyme involved in the biosynthesis of L-rhamnose, of Mtb cell wall. This study aims to derive a 3D structure of RmlA by using a comparative modeling approach. Structural refinement and energy minimization of the built model have been done with molecular dynamics. The reliability assessment of the built model was carried out with various protein checking tools such as Procheck, Whatif, ProsA, Errat, and Verify 3D. The obtained model investigates the relation between the structure and function. Molecular docking interactions of Mtb-RmlA with modified EMB (ethambutol) ligands and natural substrate have revealed specific key residues Arg13, Lys23, Asn109, and Thr223 which play an important role in ligand binding and selection. Compared to all EMB ligands, EMB-1 has shown better interaction with Mtb-RmlA model. The information thus discussed above will be useful for the rational design of safe and effective inhibitors specific to RmlA enzyme pertaining to the treatment of tuberculosis.

scholarly journals N-linked Oligosaccharides Affect the Enzymatic Activity of CD39: Diverse Interactions between Seven N-linked Glycosylation Sites

2005 ◽  
Vol 16 (4) ◽  
pp. 1661-1672 ◽  
Author(s):  
James J. Wu ◽  
Lisa E. Choi ◽  
Guido Guidotti
Keyword(s):  
Enzymatic Activity ◽  
Surface Expression ◽  
Structure And Function ◽  
Surface Appearance ◽  
C Terminus ◽  
Glycosylation Sites ◽  
N Terminus ◽  
Membrane Bound ◽  
And Function ◽  
Diverse Interactions

Rat CD39, a membrane-bound ectonucleoside triphosphate diphosphohydrolase that hydrolyzes extracellular nucleoside tri- and diphosphates, has seven potential N-glycosylation sites at asparagine residues 73, 226, 291, 333, 375, 429, and 458. To determine their roles in the structure and function of CD39, we mutated these sites individually or in combination by replacing asparagine with serine or glutamine and analyzed the surface expression and the enzymatic activity of the mutants. The results indicate that rat CD39 can be glycosylated at all seven sites when expressed in COS7 cells. Glycosylation sites 73 at the N terminus, 333 in the middle, and 429 and 458 at the C terminus were principally required for cell surface appearance of enzymatically active CD39. Whereas deletion of these sites individually had modest effects on surface ATPase activity, some double deletions of these sites had major effects on both surface activity and expression. The importance of these N-glycosylation sites is recognizable in other members of the ectonucleoside triphosphate diphosphohydrolase family.

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