کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8335993 | 1540285 | 2011 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Structural analysis of a group III Glu62-phospholipase A2 from the scorpion, Mesobuthus tamulus: Targeting and reversible inhibition by native peptides
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Structural analysis of a group III Glu62-phospholipase A2 from the scorpion, Mesobuthus tamulus: Targeting and reversible inhibition by native peptides Structural analysis of a group III Glu62-phospholipase A2 from the scorpion, Mesobuthus tamulus: Targeting and reversible inhibition by native peptides](/preview/png/8335993.png)
چکیده انگلیسی
Group III phospholipase A2 enzyme transcript from the Mesobuthus tamulus (Indian red scorpion) codes for three distinct products that include a large enzymatic subunit, a pentameric peptide and a small non-enzymatic subunit. The structures of these two subunits were modeled based on their sequence identity to bee venom PLA2 and the partial sequence of MU2 adaptin subunit of AP2 clathrin adaptor, respectively. The enzymatic subunit comprises of three helices, the calcium binding loop and a substrate binding hydrophobic channel where the structure is stabilized by four disulfide bonds. The active site of the enzyme shows a catalytic histidine residue. Interestingly, there is a conservative mutation of the conserved aspartic acid, a classical participant of catalysis in this enzyme family, to glutamic acid. However, the side chain oxygen atoms of this glutamate are oriented away from the catalytic histidine implicating the non-participation of this residue in stabilizing the tautomeric conformation of the histidine. The acidic non-enzymatic subunit comprises of extensive hydrophobic residues with a conformation of an anti-parallel β-sheets making it ideal for tissue specific targeting. The native pentapeptide with the sequence Alanine-Arginine-Serine-Alanine-Arginine was docked to the enzymatic subunit. The peptide ligand occupies the hydrophobic cavity and makes a plethora of interactions with the residues in the channel, including a hydrogen bond with the crucial catalytic histidine and coordinate bond with the calcium ion. This ligand has a binding constant (KD) of 1.5 μM. This makes the ligand a potential reversible inhibitor, ideal to prevent the enzyme from interacting with non-specific molecules enroute to the target. The enzyme-ligand complex also provides a model to understand the stereochemistry required for the design of more potent drug molecules against such enzyme drug targets.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Journal of Biological Macromolecules - Volume 48, Issue 3, 1 April 2011, Pages 423-431
Journal: International Journal of Biological Macromolecules - Volume 48, Issue 3, 1 April 2011, Pages 423-431
نویسندگان
Gururao Hariprasad, Manoj Kumar, Alagiri Srinivasan, Punit Kaur, Tej Pal Singh, Othayoth Jithesh,