Unexpected Nanomolar Inhibition of Carbonic Anhydrase by COX-2-Selective Celecoxib:  New Pharmacological Opportunities Due to Related Binding Site Recognition

2004 ◽  
Vol 47 (3) ◽  
pp. 550-557 ◽  
Author(s):  
Alexander Weber ◽  
Angela Casini ◽  
Andreas Heine ◽  
Daniel Kuhn ◽  
Claudiu T. Supuran ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Binding Site ◽  
Cox 2 ◽  
Site Recognition

scholarly journals Determinants for DNA-binding site recognition by the glucocorticoid receptor.

1992 ◽  
Vol 267 (35) ◽  
pp. 24941-24947
Author(s):  
J Zilliacus ◽  
A.P. Wright ◽  
U Norinder ◽  
J.A. Gustafsson ◽  
J Carlstedt-Duke
Keyword(s):  
Dna Binding ◽  
Glucocorticoid Receptor ◽  
Binding Site ◽  
Dna Binding Site ◽  
Site Recognition

scholarly journals Transcriptional activation by FNR and CRP: reciprocity of binding‐site recognition

1997 ◽  
Vol 23 (4) ◽  
pp. 835-845 ◽  
Author(s):  
Gary Sawers ◽  
Manuela Kaiser ◽  
Agnieszka Sirko ◽  
Martin Freundlich
Keyword(s):  
Binding Site ◽  
Transcriptional Activation ◽  
Site Recognition

Effect of the hydrogen bond network in carbonic anhydrase II zinc binding site. A theoretical study

1998 ◽  
Vol 76 (7) ◽  
pp. 1027-1032 ◽  
Author(s):  
Silvia Álvarez-Santos ◽  
Àngels González-Lafont ◽  
José M Lluch
Keyword(s):  
Hydrogen Bond ◽  
Carbonic Anhydrase ◽  
Binding Site ◽  
Zinc Binding ◽  
Carbonic Anhydrase Ii ◽  
Am1 Method ◽  
Hydrogen Bond Network ◽  
Zinc Binding Site ◽  
Bond Network ◽  
Metal Ligand

The hydrogen bond network influence on the carbonic anhydrase II (CAII) zinc binding site has been studied theoretically by using the semiempirical AM1 method. To this aim, quantum mechanical reduced models of wild-type CAII and several CAII variants have been constructed. We have shown that, when a direct metal ligand donates a hydrogen bond to an indirect metal ligand, the first-shell residues enhance their electrostatic interaction with the zinc cation. Thus, the hydrogen-bond network is able to modulate the zinc binding affinity and the zinc-water pKa.Key words: hydrogen bond network, carbonic anhydrase II, Zn2+ metalloenzyme ligands.

LIBRA: LIgand Binding site Recognition Application

2015 ◽  
pp. btv489 ◽  
Author(s):  
Le Viet Hung ◽  
Silvia Caprari ◽  
Massimiliano Bizai ◽  
Daniele Toti ◽  
Fabio Polticelli
Keyword(s):  
Ligand Binding ◽  
Binding Site ◽  
Ligand Binding Site ◽  
Site Recognition

scholarly journals Structural Characterization of Carbonic Anhydrase VIII and Effects of Missense Single Nucleotide Variations to Protein Structure and Function

2020 ◽  
Vol 21 (8) ◽  
pp. 2764
Author(s):  
Taremekedzwa Allan Sanyanga ◽  
Özlem Tastan Bishop
Keyword(s):  
Carbonic Anhydrase ◽  
Binding Site ◽  
Cross Correlation ◽  
Structure And Function ◽  
The Body ◽  
Conformational Sampling ◽  
Nucleotide Polymorphisms ◽  
Ip3 Receptor ◽  
Single Nucleotide ◽  
And Function

Human carbonic anhydrase 8 (CA-VIII) is an acatalytic isoform of the α -CA family. Though the protein cannot hydrate CO2, CA-VIII is essential for calcium (Ca2+) homeostasis within the body, and achieves this by allosterically inhibiting the binding of inositol 1,4,5-triphosphate (IP3) to the IP3 receptor type 1 (ITPR1) protein. However, the mechanism of interaction of CA-VIII to ITPR1 is not well understood. In addition, functional defects to CA-VIII due to non-synonymous single nucleotide polymorphisms (nsSNVs) result in Ca2+ dysregulation and the development of the phenotypes such as cerebellar ataxia, mental retardation and disequilibrium syndrome 3 (CAMRQ3). The pathogenesis of CAMRQ3 is also not well understood. The structure and function of CA-VIII was characterised, and pathogenesis of CAMRQ3 investigated. Structural and functional characterisation of CA-VIII was conducted through SiteMap and CPORT to identify potential binding site residues. The effects of four pathogenic nsSNVs, S100A, S100P, G162R and R237Q, and two benign S100L and E109D variants on CA-VIII structure and function was then investigated using molecular dynamics (MD) simulations, dynamic cross correlation (DCC) and dynamic residue network (DRN) analysis. SiteMap and CPORT analyses identified 38 unique CA-VIII residues that could potentially bind to ITPR1. MD analysis revealed less conformational sampling within the variant proteins and highlighted potential increases to variant protein rigidity. Dynamic cross correlation (DCC) showed that wild-type (WT) protein residue motion is predominately anti-correlated, with variant proteins showing no correlation to greater residue correlation. DRN revealed variant-associated increases to the accessibility of the N-terminal binding site residues, which could have implications for associations with ITPR1, and further highlighted differences to the mechanism of benign and pathogenic variants. SNV presence is associated with a reduction to the usage of Trp37 in all variants, which has implications for CA-VIII stability. The differences to variant mechanisms can be further investigated to understand pathogenesis of CAMRQ3, enhancing precision medicine-related studies into CA-VIII.

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