Flavour binding mechanism between a typical meat flavour compound (nonanal) and porcine myofibrillar proteins with consideration of conformational changes

2018 ◽  
Vol 53 (8) ◽  
pp. 1954-1961 ◽  
Author(s):  
Yurui Han ◽  
Hui Shen ◽  
Mouming Zhao ◽  
Weizheng Sun
Keyword(s):  
Conformational Changes ◽  
Myofibrillar Proteins ◽  
Binding Mechanism ◽  
Flavour Compound

scholarly journals Insights into the Binding Mechanism of Polyphenols and Fish Myofibrillar Proteins Explored Using Multi-spectroscopic Methods

2020 ◽  
Vol 13 (5) ◽  
pp. 797-806
Author(s):  
Wanlin Xie ◽  
Yuan Huang ◽  
Yuanzhi Xiang ◽  
Shanbai Xiong ◽  
Anne Manyande ◽  
...  
Keyword(s):  
Spectroscopic Methods ◽  
Myofibrillar Proteins ◽  
Binding Mechanism

scholarly journals An Induced Fit Conformational Change Underlies the Binding Mechanism of the Heme Transport Proteobacteria-Protein HemS

2006 ◽  
Vol 281 (43) ◽  
pp. 32606-32610 ◽  
Author(s):  
Sabine Schneider ◽  
Katherine H. Sharp ◽  
Paul D. Barker ◽  
Max Paoli
Keyword(s):  
Conformational Changes ◽  
Structural Data ◽  
Binding Pocket ◽  
Bound State ◽  
Uptake System ◽  
Heme Binding ◽  
Binding Mechanism ◽  
Induced Fit ◽  
Heme Transport ◽  
Β Sheet

Bacteria rely on their environment and/or host to acquire iron and have evolved specialized systems to sequester and transport heme. The heme uptake system HemRSTUV is common to proteobacteria, and a major challenge is to understand the molecular mechanism of heme binding and transfer between the protein molecules that underlie this heme transport relay process. In the Gram-negative pathogen Yersinia enterocolitica, the HemRSTUV system culminates with the cytoplasmic recipient HemS, which stores and delivers heme for cellular needs. HemS belongs to a family of proteins essential and unique to proteobacteria. Here we report on the binding mechanism of HemS based on structural data from its apo- and ligand-loaded forms. This heme carrier protein associates with its cargo through a novel, partly preformed binding pocket, formed between a large β-sheet dome and a three-helix subdomain. In addition to a histidine interacting with the iron, the complex is stabilized by a distal non-coordinating arginine that packs along the porphyrin plane and extensive electrostatic contacts that firmly anchor the heme propionate groups within the protein. Comparison of apo- and ligand-bound HemS crystal structures reveals striking conformational changes that underlie a “heme-induced fit” binding mechanism. Local shifts in amino acid positions combine with global, rigid body-like domain movements, and together, these bring about a switch from an open, apo-form to a closed, bound state. This is the first report in which both liganded and unliganded forms of a heme transport protein are described, thus providing penetrating insights into its mechanism of heme binding and release.

scholarly journals Structural Basis for 2′-5′-Oligoadenylate Binding and Enzyme Activity of a Viral RNase L Antagonist

2015 ◽  
Vol 89 (13) ◽  
pp. 6633-6645 ◽  
Author(s):  
Kristen M. Ogden ◽  
Liya Hu ◽  
Babal K. Jha ◽  
Banumathi Sankaran ◽  
Susan R. Weiss ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Conformational Changes ◽  
Cellular Response ◽  
Substrate Binding ◽  
Core Structure ◽  
Structural Basis ◽  
Rnase L ◽  
Binding Mechanism ◽  
Oligoadenylate Synthetase ◽  
Terminal Domain

ABSTRACTSynthesis of 2′-5′-oligoadenylates (2-5A) by oligoadenylate synthetase (OAS) is an important innate cellular response that limits viral replication by activating the latent cellular RNase, RNase L, to degrade single-stranded RNA. Some rotaviruses and coronaviruses antagonize the OAS/RNase L pathway through the activity of an encoded 2H phosphoesterase domain that cleaves 2-5A. These viral 2H phosphoesterases are phylogenetically related to the cellular A kinase anchoring protein 7 (AKAP7) and share a core structure and an active site that contains two well-defined HΦ(S/T)Φ (where Φ is a hydrophobic residue) motifs, but their mechanism of substrate binding is unknown. Here, we report the structures of a viral 2H phosphoesterase, the C-terminal domain (CTD) of the group A rotavirus (RVA) VP3 protein, both alone and in complex with 2-5A. The domain forms a compact fold, with a concave β-sheet that contains the catalytic cleft, but it lacks two α-helical regions and two β-strands observed in AKAP7 and other 2H phosphoesterases. The cocrystal structure shows significant conformational changes in the R loop upon ligand binding. Bioinformatics and biochemical analyses reveal that conserved residues and residues required for catalytic activity and substrate binding comprise the catalytic motifs and a region on one side of the binding cleft. We demonstrate that the VP3 CTD of group B rotavirus, but not that of group G, cleaves 2-5A. These findings suggest that the VP3 CTD is a streamlined version of a 2H phosphoesterase with a ligand-binding mechanism that is shared among 2H phosphodiesterases that cleave 2-5A.IMPORTANCEThe C-terminal domain (CTD) of rotavirus VP3 is a 2H phosphoesterase that cleaves 2′-5′-oligoadenylates (2-5A), potent activators of an important innate cellular antiviral pathway. 2H phosphoesterase superfamily proteins contain two conserved catalytic motifs and a proposed core structure. Here, we present structures of a viral 2H phosphoesterase, the rotavirus VP3 CTD, alone and in complex with its substrate, 2-5A. The domain lacks two α-helical regions and β-strands present in other 2H phosphoesterases. A loop of the protein undergoes significant structural changes upon substrate binding. Together with our bioinformatics and biochemical findings, the crystal structures suggest that the RVA VP3 CTD domain is a streamlined version of a cellular enzyme that shares a ligand-binding mechanism with other 2H phosphodiesterases that cleave 2-5A but differs from those of 2H phosphodiesterases that cleave other substrates. These findings may aid in the future design of antivirals targeting viral phosphodiesterases with cleavage specificity for 2-5A.

scholarly journals Binding mechanism and dynamic conformational change of C subunit of PKA with different pathways

2017 ◽  
Vol 114 (38) ◽  
pp. E7959-E7968 ◽  
Author(s):  
Wen-Ting Chu ◽  
Xiakun Chu ◽  
Jin Wang
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Conformational Change ◽  
Conformational Changes ◽  
Coarse Grained ◽  
Binding Mechanism ◽  
Induced Fit ◽  
C Subunit ◽  
Dynamics Simulations ◽  
Substrate Inhibitor

The catalytic subunit of PKA (PKAc) exhibits three major conformational states (open, intermediate, and closed) during the biocatalysis process. Both ATP and substrate/inhibitor can effectively induce the conformational changes of PKAc from open to closed states. Aiming to explore the mechanism of this allosteric regulation, we developed a coarse-grained model and analyzed the dynamics of conformational changes of PKAc during binding by performing molecular dynamics simulations forapoPKAc, binary PKAc (PKAc with ATP, PKAc with PKI), and ternary PKAc (PKAc with ATP and PKI). Our results suggest a mixed binding mechanism of induced fit and conformational selection, with the induced fit dominant. The ligands can drive the movements of Gly-rich loop as well as some regions distal to the active site in PKAc and stabilize them at complex state. In addition, there are two parallel pathways (pathway with PKAc-ATP as an intermediate and pathway PKAc-PKI as an intermediate) during the transition from open to closed states. By molecular dynamics simulations and rate constant analyses, we find that the pathway through PKAc-ATP intermediate is the main binding route from open to closed state because of the fact that the bound PKI will hamper ATP from successful binding and significantly increase the barrier for the second binding subprocess. These findings will provide fundamental insights of the mechanisms of PKAc conformational change upon binding.

Characterization of the binding mechanism and conformational changes of bovine serum albumin upon interaction with aluminum-maltol: a spectroscopic and molecular docking study

Metallomics ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1625-1634 ◽  
Author(s):  
Dai Cheng ◽  
Xuerui Wang ◽  
Jinlei Tang ◽  
Xinyu Zhang ◽  
Chunling Wang ◽  
...  
Keyword(s):  
Drinking Water ◽  
Molecular Docking ◽  
Conformational Changes ◽  
Human Exposure ◽  
Health Hazard ◽  
Docking Study ◽  
Human Beings ◽  
Binding Mechanism ◽  
Molecular Docking Study

The widespread use of aluminum in the treatment of drinking water, food, agriculture and pharmaceuticals has greatly increased the risk of human exposure to excess aluminum, which is a serious health hazard to human beings.

Structure ofD-alanine-D-alanine ligase fromYersinia pestis: nucleotide phosphate recognition by the serine loop

2016 ◽  
Vol 72 (1) ◽  
pp. 12-21 ◽  
Author(s):  
Huyen-Thi Tran ◽  
Myoung-Ki Hong ◽  
Ho-Phuong-Thuy Ngo ◽  
Kim-Hung Huynh ◽  
Yeh-Jin Ahn ◽  
...  
Keyword(s):  
Enzyme Kinetics ◽  
Conformational Changes ◽  
Binding Sites ◽  
Drug Target ◽  
Antibacterial Agents ◽  
Binding Mechanism ◽  
Bacterial Peptidoglycan ◽  
Loop 2 ◽  
Hydrolysis Of ◽  
Important Drug

D-Alanyl-D-alanine is an essential precursor of bacterial peptidoglycan and is synthesized by D-alanine-D-alanine ligase (DDL) with hydrolysis of ATP; this reaction makes DDL an important drug target for the development of antibacterial agents. Five crystal structures of DDL fromYersinia pestis(YpDDL) were determined at 1.7–2.5 Å resolution: apo, AMP-bound, ADP-bound, adenosine 5′-(β,γ-imido)triphosphate-bound, and D-alanyl-D-alanine- and ADP-bound structures. YpDDL consists of three domains, in which four loops, loop 1, loop 2 (the serine loop), loop 3 (the ω-loop) and loop 4, constitute the binding sites for two D-alanine molecules and one ATP molecule. Some of them, especially the serine loop and the ω-loop, show flexible conformations, and the serine loop is mainly responsible for the conformational change in substrate nucleotide phosphates. Enzyme-kinetics assays were carried out for both the D-alanine and ATP substrates and a substrate-binding mechanism was proposed for YpDDL involving conformational changes of the loops.

Understanding the Binding Mechanism of Antagonist (AZD3293) Against BACE-1: Molecular Insights into Alzheimer’s Drug Discovery

2020 ◽  
Vol 17 (7) ◽  
pp. 850-857
Author(s):  
Sphelele Sosibo ◽  
Daniel Gyamfi Amoako ◽  
Anou Moise Somboro ◽  
Darren Delai Sun ◽  
Jane Catherine Ngila ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Root Mean Square ◽  
Conformational Changes ◽  
Radius Of Gyration ◽  
Mean Square ◽  
Binding Mechanism ◽  
Ligand Complex ◽  
Bace 1

Background: β-site amyloid precursor protein cleaving enzyme (BACE 1) is the ratelimiting enzyme in the formation of neurotoxic β-amyloid (Aβ) residues (Aβ1-40 or Aβ1-42) considered as key players in the onset of Alzheimer’s Disease (AD). Consequently, BACE 1 is one of the principal targets of anti-AD therapy with many small molecule BACE 1 inhibitors (BACE 1Is) in clinical trials. AZD3293 (Lanabecestat) is a BACE 1I that concluded in phase 2/3 clinical trials. Due to the limited knowledge about the interaction of this drug with the BACE 1 enzyme, in the present study, we performed comprehensive Molecular Dynamics (MD) analysis to understand the binding mechanism of AZD3293 to BACE 1. Methods: A production run of 120 ns is carried out and results are analysed using Root Mean Square Deviation (RMSD), root mean square fluctuation (RMSF), and radius of gyration (Rg) to explain the stability of enzyme ligand complex. Further, the distance (d1) between the flap tip (Thr72) and the hinge residue of the flexible loop (Thr328), in relation to θ1 (Thr72–Asp228- Thr328), and to the dihedral angle δ (Thr72-Asp35-Asp228-Thr328) were measured. Results: The presence of the ligand within the active site restricted conformational changes as shown by decreased values of RMSF and average RMSD of atomic positions when compared to the values of the apoenzyme. Further analysis via the flap dynamics approach revealed that the AZD3293 decreases the flexibility of binding residues and made them rigid by altering the conformational changes. Conclusion: The prospective binding modes of AZD3293 from this study may extend the knowledge of the BACE 1-drug interaction and pave the way to design analogues with similar inhibitory properties needed to slow the progression of Alzheimer’s disease.

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