Computer modelling of human carbonic anhydrase II.

by Nicholas Richard Jones

Publisher: University of Manchester in Manchester

Written in English
Published: Pages: 101 Downloads: 951
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Edition Notes

Thesis (M.Sc.), - University of Manchester, Department of Chemistry.

ContributionsUniversity of Manchester. Department of Chemistry.
The Physical Object
Pagination101p.
Number of Pages101
ID Numbers
Open LibraryOL16576221M

Reversible hydration of carbon dioxide. May stimulate the sodium/bicarbonate transporter activity of SLC4A4 that acts in pH homeostasis. It is essential for acid overload removal from the retina and retina epithelium, and acid release in the choriocapillaris in the choroid. Figure - Human carbonic anhydrase II viewed as a CPK model. The zinc ion is the green sphere at the bottom of the active site. The color codes for the other atoms are: C = white, H = cyan, N = blue, O = red, S = yellow. Essential for bone resorption and osteoclast differentiation (By similarity). Reversible hydration of carbon dioxide. Can hydrates cyanamide to urea. Involved in the regulation of fluid secretion into the anterior chamber of the eye.   A new model for catalysis of human carbonic anhydrase II is suggested. The model is based on the X-ray structure of the hydrogen bond network in the catalytic site. The outer part of the network is proposed to adjust the p K a of the catalytic site to the experimentally observed value of about 7. The inner part of the network is proposed to become a low-barrier .

The application of chemoinformatics in the drug discovery process is today a wide field of theoretical and applied research. Ab initio mol. dynamics (AIMD) and combined Hybrid/AIMD simulations appear as promising candidates for an in situ modeling of enzymic reactions. In order to probe the capabilities of these methods for the characterization of enzymic processes we have chosen the enzyme Human Carbonic Anhydrase II (HCAII) as a test case system. Several models of the active site have Cited by: 2. Human Carbonic Anhydrase II (Hca II) Words | 4 Pages. Human Carbonic anhydrase II Carbonic anhydrase (CA, EC ) has around 16 isozymes, which are different isoforms, and these have assorted tissue position 's subcellular and distribution, which are exist in plants, animal, archaea, and eubacteria. (Chromatronix Inc., Berkeley, Calif.) and an Infotronic model CRS 1lOA integrator (Infotronic Corp., Houston, Tex). Tryptic Hydrolysis of Amidinated Carbonic Anhydrase C-To restrict tryptic hydrolysis to arginyl bonds, the c-amino groups of lysine side chains in human carbonic anhydrase C were modified by the.

ApplicationPotent carbonic anhydrase II (CAII) inhibitors for drug discovery and a method for designing BenefitsHighly potent molecules for inhibiting carbonic anhydrase. Compounds generated using a novel computational chemistry method based on a validated data retrieval platform. Carbonic anhydrase activity and dysfunction is also associated with mental retardation, Alzheimer′s disease, and aging. The expression of certain carbonic anhydrase isoforms have been linked with the agressiveness and prognosis of various human cancers, including renal, colon, and lung. Carbonic anhydrase, enzyme found in red blood cells, gastric mucosa, pancreatic cells, and renal tubules that catalyzes the interconversion of carbon dioxide (CO2) and carbonic acid (H2CO3). Carbonic anhydrase plays an important role in respiration by influencing CO2 transport in the blood. The. AbstractThe synthesis of a new series of sulfamides incorporating ortho-, meta, and para-benzenesulfamide moieties is reported, which were investigated for the inhibition of two human (h) isoforms of the zinc enzyme carbonic anhydrase (CA, EC ), hCA I and II, and two Vibrio cholerae enzymes, belonging to the α- and β-CA classes (VchCAα, VchCAβ).Cited by: 4.

Computer modelling of human carbonic anhydrase II. by Nicholas Richard Jones Download PDF EPUB FB2

An interactive human carbonic anhydrase-II (hCA-II) receptor--pharmacophore molecular model & anti-convulsant activity of the designed and synthesized 5-amino-1,3,4-thiadiazolethiol conjugated imine derivatives. Yusuf M(1), Khan RA, Khan M, Ahmed by: The development of efficient biocatalysts for industry remains a challenge.

Over the past decade, the group of Professor Thomas R. Ward (University of Basel, Switzerland) has developed various artificial metalloenzymes for enantioselective catalysis. For this purpose, a biotinylated organometallic catalyst is incorporated in (Strept)avidin, thereby providing a hybrid catalyst Author: Fabien Monnard.

Subnanomolar Inhibitors from Computer Screening: A Model Study Using Human Carbonic Anhydrase II Grueneberg, S., Wendt, B., Klebe, G. () Angew Chem Int Ed Engl Cited by: Request PDF | Subnanomolar Inhibitors from Computer Screening: A Model Study Using Human Carbonic Anhydrase II | FlexX and DrugScore are the two computer programs which were applied finally to.

Using Covalent Dimers of Human Carbonic Anhydrase II To Model Bivalency in Immunoglobulins Eric T. Mack, Phillip W. Snyder, Raquel Perez-Castillejos, and George M. Whitesides * Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MassachusettsUnited States.

Folding and Stability of the N-Terminus of Human Carbonic Anhydrase IICited by: Keywords:Carbonic anhydrase, Balaban indices, QSAR, topological index, quantum-theoritical descriptor, human CA II.

Abstract: Mathematical models were developed for the estimation of human carbonic anhydrase (CA) II inhibition. A large set of 95 CA inhibitors incorporating diverse aromatic rings were used for this by: 2. [Show full abstract] rigidity of human carbonic anhydrase II (HCA II; EC ) via incorporation of proline residues at positions and.

A potential function was generated from these observations and used to evaluate models for novel disulfide bonds in human carbonic anhydrase II (HCAII).

Three double-cysteine variants of HCAII were purified and the effective concentrations of their thiol groups were determined by titrations with glutathione and by: DFT-Based QSAR Modelling of Inhibitory Activity of Coumarins and Sulfocoumarins on Carbonic Anhydrase Computer modelling of human carbonic anhydrase II.

book Isoforms (CA I and CA II) Author(s): Erol Eroglu*. Department of Mathematics and Sciences Education, Faculty of Education, Akdeniz University, Dumlupınar Bulvarı, KampusAntalya, TurkeyCited by: 1. 1KWQ: HUMAN CARBONIC ANHYDRASE II COMPLEXED WITH INHIBITOR A new strategy is described to search for possible leads of human carbonic anhydrase II, applying a protocol of several consecutive hierarchical filters involving a preselection based on functional group requirements and fast pharmacophore matching.

A Model Study Using Cited by: “Using Covalent Dimers of Human Carbonic Anhydrase II to Model Bivalency in Immunoglubulins.” J.

Amer. Chem. Soc.,Pp. Using Covalent Dimers of Human Carbonic Anhydrase II to Model Bivalency in Immunoglubulins |. About this book. Introduction. Carbonic anhydrase (CA) is a seemingly ubiquitous enzyme of profound physiological importance, which plays essential roles in respiration, acid-base homeostasis, bone resorption, calcification, photosynthesis, several biosynthetic pathways and a variety of processes involving ion, gas and fluid transfer.

Fragment screening is a powerful tool to identify and characterize binding pockets in proteins. We herein present the results of a proof-of-concept screening campaign of a versatile entry fragment library from our laboratory against the drug target and model protein human carbonic anhydrase II.

The screening revealed a novel chemotype for carbonic anhydrase inhibition. “ Carbonic Anhydrase as a Model for Biophysical and Physical-Organic Studies of Proteins and Protein-Ligand Binding.” Chemical Reviews,Pp. pdf Function of Carbonic Anhydrase •The carbonic anhydrases (CA) form a family of enzymes that catalyze: •The transport of CO 2 around the respiratory system is vital, however the solubility of CO 2 in water at physiological conditions is very small •Carbonic anhydrase enhances the solubility of CO 2 by catalyzing its conversion to the more soluble HCOFile Size: 1MB.

The theoretical models had good reliability (R 2 >) and predictability (Q 2 >), and the contour maps could graphically present the contributions of the force fields for activity and identify the structural divergence between human carbonic anhydrase II inhibitors and human carbonic anhydrase IX inhibitors.

Consequently, we explored the Cited by: 1. Key Features. Offers comprehensive coverage of the carbonic anhydrases enzyme family and their properties as biocatalysts.

Includes current applications of carbonic anhydrases in biotechnology on the basis of their catalytic efficiency, including new technologies for CO2 capture processes. Identifies new targets for drug design. Carbonic anhydrases have been found in all kingdoms of life.

Carbonic anhydrase has 3 different classes: alpha, beta and gamma which share very little sequence or structural similarity, thus far they all perform the same function and require a zinc ion at the active site. Mammalian carbonic anhydrase is monomeric and belongs to the alpha class. Molecular dynamics (MD) simulations, in combination with the Markov-state model (MSM), were applied to probe CO 2 diffusion from an aqueous solution into the active site of human carbonic anhydrase II (hCA-II), an enzyme useful for enhanced CO 2 capture and utilization.

The diffusion process in the hydrophobic pocket of hCA-II was illustrated in terms of a two-dimensional free. Carbonic Anhydrase II.

Carbonic anhydrases form a family of enzymes classified as metalloproteases, because their active site contains a zinc ion and is able to catalyze the reversible hydration of carbon dioxide to generate a proton and a bicarbonate ion.

Carbonic anhydrase II (CAII) is the only soluble form of the enzyme and regulates the acid–base. The approach of CO2 to a series of active site model complexes of human carbonic anhydrase II (HCAII) and its catalytic hydration to bicarbonate anion have been investigated using semiempirical MO theory (AM1).

The results show that direct nucleophilic attack of zinc-bound hydroxide to the substrate carbon occurs in each model by: Human Carbonic Anhydrase.

Product # Description. Add to Cart. C Carbonic Anhydrase II human recombinant, expressed in E. coli, buffered aqueous solution: pricing. C Carbonic Anhydrase I from human erythrocytes: pricing. C Carbonic Anhydrase I from human erythrocytes Isoelectric focusing marker, pI This book offers deep insights into the thermodynamics and molecular structures of the twelve catalytically active isoforms of human carbonic anhydrase (CA) with a particular focus on inhibitor binding for drug design.

Illustrated with numerous X-ray crystallographic structures. A single-base-pair deletion in exon 7 of the human carbonic anhydrase II gene was found to be the molecular defect in a group of independently ascertained, clinically heterogeneous, Hispanic carbonic anhydrase II-deficient patients, all of whom had ancestors from the Caribbean islands.

This mutation predicts a +1 frameshift at codon and Cited by: Carbonic anhydrases (CAs) are a large family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide. They participate in a variety of biological processes, including respiration, calcification, acid-base balance, bone resorption, and the formation of aqueous humor, cerebrospinal fluid, saliva, and gastric s: CA12, CAXII, HsT, CA-XII.

Ethoxyzolamide is a cell-permeant sulfonamide inhibitor of carbonic anhydrase activity (8, 26). If CAH1 enhances carbon assimilation through its carbonic anhydrase activity, we predicted that treatment of cells with ethoxyzolamide would cause defects in photosynthetic carbon assimilation similar to those seen in the cah1 by: View protein in InterPro IPR Alpha_CA_VII IPR CA_dom IPR CA_dom_sf IPR Carbonic_anhydrase_a-class IPR Carbonic_anhydrase_a-class_CS: PANTHER i: PTHR PTHR, 1 hit: Pfam i: View protein in Pfam PF Carb_anhydrase, 1 hit.

A series of benzamides incorporating 4-sulfamoyl moieties were obtained by reacting 4-sulfamoyl benzoic acid with primary and secondary amines and amino acids. These sulfonamides were investigated as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC ).

The human (h) isoforms hCA II, VII, and IX were inhibited in the low nanomolar or subnanomolar Cited by: 3. Ribbon diagram of human carbonic anhydrase II, with zinc ion visible in the center.

The carbonic anhydrases (or carbonate dehydratases) form a family of enzymes that catalyze the interconversion between carbon dioxide and water and the dissociated ions of carbonic acid (i.e. bicarbonate and hydrogen ions).BRENDA: BRENDA entry.

Chapter 1: Human carbonic anhydrase II and enzyme modelling 15 Reaction and function 15 Structure 17 Significance of pK a within the active site 21 Deep water molecule and water network 26 His and the proton shuttle mechanism 26 Mechanism of .Carbonic anhydrase (CA) catalyzes the reversible hydration and dehydration reactions of CO 2 /H 2 CO 3.

CAs are widespread in nature, being found in animals, plants, and certain bacteria. Sixteen isozymes have been identified and characterized in mammals. Carbonic anhydrase induces retinal vascular permeability. A notable finding was the identification of the intracellular enzyme CA-I in the PDR vitreous by: