User:Alisha, Deepa, Pamiz/Sandbox 1: Difference between revisions

Line 76:

The interaction between Esomeprazole and H+/K+-ATPase has not yet been crystallized.15 Data obtained from the crystallized structure of a '''SCH28080-ATPase''' provides structural and binding site information.16 SCH28080 is a competitive K+ inhibitor that interacts with the enzyme’s Phe126 residue and prevents disulfide bond formation between Omeprazole and Cys813, suggesting mutually exclusive inhibitions and an overlapping binding site.16 The crystallized structure of SCH28080-ATPase shows the same luminal-open (E2) conformation as Esomeprazole, and is the first and only crystallized evidence of PPI-ATPase binding site and conformational change.16 Using this information, the SCH28080-ATPase crystallized structure provides evidence of the two binding sites, Cys813 and Cys892.15,16

The binding pocket, as proposed using SCH28080 includes the following residues: Glu936, Lys791, Glu795, Cys813, Cys892, Phe126, and Glu822 (Figure 5). The negatively charged residues within the TM domains are important for K+ binding and are conserved in all P-type ATPases.16 The SCH28080 model shows that electrostatic and hydrophobic factors affect drug-enzyme interaction.16[[Image:pymol.jpg|300px|left|thumb| '''Crystalized Structure of H+/K+-ATPase ''' TM helices 5,6,7,8 are each highlighted in a different color; the majority of the A & B domain within the enzyme, non-catalytic portions of the enzyme, and SCH28080 have been omitted. The figure depicts the proposed binding sites of the crystallized structure of H+/K+-ATPase. Cys813 and Cys892 are highlighted as the two disulfide bond formation sites. Cys 813 is found between TM5 and TM6 domains while Cys892 is between TM7 and TM8 domains.14 Sulfenamide will interact with these two residues and form disulfide bonds. ]][[Image:pymol_2.jpg|300px|right|thumb| '''Binding pocket of SCH28080-ATPase complex''' PDB image obtained from the RCSB Protein Data Bank.15 Image created using PyMol™ Molecular Graphics System. Glu936 (orange), Glu822 (orange), Lys791 (yellow), Glu 795 (orange), Phe126 (gray), Cys892 (light blue), and Cys813 (light blue) are proposed to be part of Esomeprazole’s binding cavity.15,16 ]]

Revision as of 20:33, 6 December 2013 view source Deepa Patel (talk \| contribs) 230 edits No edit summary ← Older edit		Revision as of 20:34, 6 December 2013 view source Deepa Patel (talk \| contribs) 230 edits No edit summary Newer edit →
Line 76:		Line 76:
	The interaction between Esomeprazole and H+/K+-ATPase has not yet been crystallized.15 Data obtained from the crystallized structure of a '''SCH28080-ATPase''' provides structural and binding site information.16 SCH28080 is a competitive K+ inhibitor that interacts with the enzyme’s Phe126 residue and prevents disulfide bond formation between Omeprazole and Cys813, suggesting mutually exclusive inhibitions and an overlapping binding site.16 The crystallized structure of SCH28080-ATPase shows the same luminal-open (E2) conformation as Esomeprazole, and is the first and only crystallized evidence of PPI-ATPase binding site and conformational change.16 Using this information, the SCH28080-ATPase crystallized structure provides evidence of the two binding sites, Cys813 and Cys892.15,16		The interaction between Esomeprazole and H+/K+-ATPase has not yet been crystallized.15 Data obtained from the crystallized structure of a '''SCH28080-ATPase''' provides structural and binding site information.16 SCH28080 is a competitive K+ inhibitor that interacts with the enzyme’s Phe126 residue and prevents disulfide bond formation between Omeprazole and Cys813, suggesting mutually exclusive inhibitions and an overlapping binding site.16 The crystallized structure of SCH28080-ATPase shows the same luminal-open (E2) conformation as Esomeprazole, and is the first and only crystallized evidence of PPI-ATPase binding site and conformational change.16 Using this information, the SCH28080-ATPase crystallized structure provides evidence of the two binding sites, Cys813 and Cys892.15,16
	The binding pocket, as proposed using SCH28080 includes the following residues: Glu936, Lys791, Glu795, Cys813, Cys892, Phe126, and Glu822 (Figure 5). The negatively charged residues within the TM domains are important for K+ binding and are conserved in all P-type ATPases.16 The SCH28080 model shows that electrostatic and hydrophobic factors affect drug-enzyme interaction.16[[Image:pymol.jpg\|300px\|left\|thumb\| '''Crystalized Structure of H+/K+-ATPase ''' TM helices 5,6,7,8 are each highlighted in a different color; the majority of the A & B domain within the enzyme, non-catalytic portions of the enzyme, and SCH28080 have been omitted. The figure depicts the proposed binding sites of the crystallized structure of H+/K+-ATPase. Cys813 and Cys892 are highlighted as the two disulfide bond formation sites. Cys 813 is found between TM5 and TM6 domains while Cys892 is between TM7 and TM8 domains.14 Sulfenamide will interact with these two residues and form disulfide bonds. ]][[Image:pymol_2.jpg\|300px\|right\|thumb\| '''Binding pocket of SCH28080-ATPase complex''' PDB image obtained from the RCSB Protein Data Bank.15 Image created using PyMol™ Molecular Graphics System. Glu936 (orange), Glu822 (orange), Lys791 (yellow), Glu 795 (orange), Phe126 (gray), Cys892 (light blue), and Cys813 (light blue) are proposed to be part of Esomeprazole’s binding cavity.15,16 ]]		The binding pocket, as proposed using SCH28080 includes the following residues: Glu936, Lys791, Glu795, Cys813, Cys892, Phe126, and Glu822 (Figure 5). The negatively charged residues within the TM domains are important for K+ binding and are conserved in all P-type ATPases.16 The SCH28080 model shows that electrostatic and hydrophobic factors affect drug-enzyme interaction.16[[Image:pymol.jpg\|300px\|left\|thumb\| '''Crystalized Structure of H+/K+-ATPase ''' TM helices 5,6,7,8 are each highlighted in a different color; the majority of the A & B domain within the enzyme, non-catalytic portions of the enzyme, and SCH28080 have been omitted. The figure depicts the proposed binding sites of the crystallized structure of H+/K+-ATPase. Cys813 and Cys892 are highlighted as the two disulfide bond formation sites. Cys 813 is found between TM5 and TM6 domains while Cys892 is between TM7 and TM8 domains.14 Sulfenamide will interact with these two residues and form disulfide bonds. ]][[Image:pymol_2.jpg\|300px\|right\|thumb\| '''Binding pocket of SCH28080-ATPase complex''' PDB image obtained from the RCSB Protein Data Bank.15 Image created using PyMol™ Molecular Graphics System. Glu936 (orange), Glu822 (orange), Lys791 (yellow), Glu 795 (orange), Phe126 (gray), Cys892 (light blue), and Cys813 (light blue) are proposed to be part of Esomeprazole’s binding cavity.15,16 ]]