Compatibility of the Ligand Binding Sites in the Spike Glycoprotein of COVID-19 with those in the Aminopeptidase and the Caveolins 1, 2 Proteins

2021 ◽  
pp. 4760-4766
Author(s):  
Ali Adel Dawood ◽  
Mahmood Abduljabar Altobje ◽  
Haitham Abdul-Malik Alnori
Keyword(s):  
Ligand Binding ◽  
Viral Entry ◽  
Binding Sites ◽  
In Silico Analysis ◽  
Cell Receptor ◽  
Spike Glycoprotein ◽  
Strong Response ◽  
Interaction Sites ◽  
Ligand Binding Sites ◽  
Interaction Domains

A novel severe viral pneumonia emerged in Wuhan city, China, in December 2019. The spike glycoprotein of the SARS-CoV-2 plays a crucial role in the viral entry to the host cell and eliciting a strong response for antibody-mediated neutralization in mice. Caveolins 1,2 are scaffolding proteins dovetailed as a co-stimulatory signal essential for T-cell receptor and activation. Aminopeptidase is a membrane protein acting as a receptor for human coronavirus within the S1 subunit of the spike glycoprotein. Vaccines for COVID-19 have become a priority for predisposition against the outbreak, so that our study aimed to find interaction sites between SP of SARS-CoV-2 and CAV1, CAV2, and AMPN. Methods: Amino acids motif search was employed to predict the possible CAV1, CAV2, and AMPN related interaction domains in the SARS-CoV-2 SP In silico analysis. Results: Interactions between proteins revealed 5 and16 residues. ZN ligand binding site is matched between AMPN and SARS- CoV-2 SP. HLA-A*74:01 allele is the best CTL epitope for SP. We identified seven B-cell epitopes specifically for SARS-CoV-2 SP. Conclusions: SARS-CoV-2 SP binding sites might be compatible with AMPN ligand binding sites. The limit score was detected for ligand binding sites of CAV1 and CAV2. Our findings might be critical for the further substantial study of vaccine production strategy.

scholarly journals Non-catalytic binding sites induce weaker long-range evolutionary rate gradients than catalytic sites in enzymes

2019 ◽  
Author(s):  
Avital Sharir-Ivry ◽  
Yu Xia
Keyword(s):  
Ligand Binding ◽  
Long Range ◽  
Binding Sites ◽  
Evolutionary Rate ◽  
Functional Sites ◽  
Interaction Sites ◽  
Catalytic Sites ◽  
Ligand Binding Sites ◽  
Different Types ◽  
Rate Gradient

AbstractEnzymes exhibit a strong long-range evolutionary constraint that extends from their catalytic site and affects even distant sites, where site-specific evolutionary rate increases monotonically with distance. While protein-protein sites in enzymes was previously shown to induce only a weak conservation gradient, a comprehensive relationship between different types of functional sites in proteins and the magnitude of evolutionary rate gradients they induce has yet to be established. Here, we systematically calculate the evolutionary rate (dN/dS) of sites as a function of distance from different types of binding sites on enzymes and other proteins: catalytic sites, non-catalytic ligand binding sites, allosteric binding sites, and protein-protein interaction sites. We show that catalytic binding sites indeed induce significantly stronger evolutionary rate gradient than all other types of non-catalytic binding sites. In addition, catalytic sites in enzymes with no known allosteric function still induce strong long-range conservation gradients. Notably, the weak long-range conservation gradients induced by non-catalytic binding sites on enzymes is nearly identical in magnitude to those induced by ligand binding sites on non-enzymes. Finally, we show that structural determinants such as local solvent exposure of sites cannot explain the observed difference between catalytic and non-catalytic functional sites. Our results suggest that enzymes and non-enzymes share similar evolutionary constraints only when examined from the perspective of non-catalytic functional sites. Hence, the unique evolutionary rate gradient from catalytic sites in enzymes is likely driven by the optimization of catalysis rather than ligand binding and allosteric functions.

scholarly journals Diversity in the structures and ligand-binding sites of nematode fatty acid and retinol-binding proteins revealed by Na-FAR-1 from Necator americanus

2015 ◽  
Vol 471 (3) ◽  
pp. 403-414 ◽  
Author(s):  
M. Florencia Rey-Burusco ◽  
Marina Ibáñez-Shimabukuro ◽  
Mads Gabrielsen ◽  
Gisela R. Franchini ◽  
Andrew J. Roe ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Ligand Binding ◽  
Tissue Distribution ◽  
Binding Sites ◽  
Binding Proteins ◽  
Retinol Binding Protein ◽  
Internal Cavity ◽  
Binding Characteristics ◽  
Necator Americanus ◽  
Ligand Binding Sites

Necator americanus fatty acid and retinol-binding protein-1 (Na-FAR-1) is an abundantly expressed FAR from a parasitic hookworm. The present work describes its tissue distribution, structure and ligand-binding characteristics and shows that Na-FAR-1 expands to transport multiple FA molecules in its internal cavity.

scholarly journals Adenosine Receptors of Cerebral Microvessels and Choroid Plexus

1986 ◽  
Vol 6 (4) ◽  
pp. 463-470 ◽  
Author(s):  
Rajesh N. Kalaria ◽  
Sami I. Harik
Keyword(s):  
Cerebral Cortex ◽  
Ligand Binding ◽  
Choroid Plexus ◽  
Adenosine Receptors ◽  
Binding Sites ◽  
Specific Binding ◽  
Cerebral Microvessels ◽  
High Affinity ◽  
Receptor Sites ◽  
Ligand Binding Sites

We studied, by ligand binding methods, the two adenosine receptors, A, and A2, in rat and pig cerebral microvessels and pig choroid plexus. Ligand binding to cerebral microvessels was compared with that to membranes of the cerebral cortex. [3H]Cyclohexyladenosine and [3H]l-phenylisopropyladenosine were the ligands used for A1-receptors, and [3H]5'- N-ethylcarboxamide adenosine ([3H]NECA) was used to assess A2-receptors. We report that cerebral microvessels and choroid plexus exhibit specific [3H]NECA binding, but have no appreciable A1-receptor ligand binding sites. Specific binding of [3H]NECA to cerebral microvessels, choroid plexus, and cerebral cortex was saturable and suggested the existence of two classes of A2-receptor sites: high-affinity ( Kd ∼ 250 n M) and low-affinity ( Kd ∼ 1–2 μ M) sites. The Kd and Bmax of NECA binding to cerebral microvessels and cerebral cortex were similar within each species. Our results, indicating the existence of A2-receptors in cerebral microvessels, are consistent with results of increased adenylate cyclase activity by adenosine and some of its analogues in these microvessels.

A naturally occurring Tyr143HisαIIb mutation abolishes αIIbβ3 function for soluble ligands but retains its ability for mediating cell adhesion and clot retraction: comparison with other mutations causing ligand-binding defects

Blood ◽  
2003 ◽  
Vol 101 (9) ◽  
pp. 3485-3491 ◽  
Author(s):  
Teruo Kiyoi ◽  
Yoshiaki Tomiyama ◽  
Shigenori Honda ◽  
Seiji Tadokoro ◽  
Morio Arai ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Ligand Binding ◽  
Binding Sites ◽  
Clot Retraction ◽  
Naturally Occurring ◽  
Binding Function ◽  
293 Cells ◽  
Ligand Binding Sites ◽  
Functional Defect ◽  
And Function

The molecular basis for the interaction between a prototypic non–I-domain integrin, αIIbβ3, and its ligands remains to be determined. In this study, we have characterized a novel missense mutation (Tyr143His) in αIIb associated with a variant of Glanzmann thrombasthenia. Osaka-12 platelets expressed a substantial amount of αIIbβ3(36%-41% of control) but failed to bind soluble ligands, including a high-affinity αIIbβ3-specific peptidomimetic antagonist. Sequence analysis revealed that Osaka-12 is a compound heterozygote for a single 521T>C substitution leading to a Tyr143His substitution in αIIb and for the null expression of αIIb mRNA from the maternal allele. Given that Tyr143 is located in the W3 4-1 loop of the β-propeller domain of αIIb, we examined the effects of Tyr143His or Tyr143Ala substitution on the expression and function of αIIbβ3 and compared them with KO (Arg-Thr insertion between 160 and 161 residues of αIIb) and with the Asp163Ala mutation located in the same loop by using 293 cells. Each of them abolished the binding function of αIIbβ3 for soluble ligands without disturbing αIIbβ3 expression. Because immobilized fibrinogen and fibrin are higher affinity/avidity ligands for αIIbβ3, we performed cell adhesion and clot retraction assays. In sharp contrast to KO mutation and Asp163AlaαIIbβ3, Tyr143HisαIIbβ3-expressing cells still had some ability for cell adhesion and clot retraction. Thus, the functional defect induced by Tyr143HisαIIb is likely caused by its allosteric effect rather than by a defect in the ligand-binding site itself. These detailed structure–function analyses provide better understanding of the ligand-binding sites in integrins.

Identification of Ligand Binding Sites on Proteins Using a Multi-Scale Approach

2002 ◽  
Vol 124 (10) ◽  
pp. 2337-2344 ◽  
Author(s):  
Meir Glick ◽  
Daniel D. Robinson ◽  
Guy H. Grant ◽  
W. Graham Richards
Keyword(s):  
Ligand Binding ◽  
Binding Sites ◽  
Multi Scale ◽  
Ligand Binding Sites
Sign in / Sign up

Export Citation Format

Share Document