'''Structure of the N298S variant of human pancreatic alpha-amylase complexed with acarbose'''
===Structure of the N298S variant of human pancreatic alpha-amylase complexed with acarbose===
==Overview==
<!--
The mechanism of allosteric activation of alpha-amylase by chloride has been studied through structural and kinetic experiments focusing on the chloride-dependent N298S variant of human pancreatic alpha-amylase (HPA) and a chloride-independent TAKA-amylase. Kinetic analysis of the HPA variant clearly demonstrates the pronounced activating effect of chloride ion binding on reaction rates and its effect on the pH-dependence of catalysis. Structural alterations observed in the N298S variant upon chloride ion binding suggest that the chloride ion plays a variety of roles that serve to promote catalysis. One of these is having a strong influence on the positioning of the acid/base catalyst residue E233. Absence of chloride ion results in multiple conformations for this residue and unexpected enzymatic products. Chloride ion and N298 also appear to stabilize a helical region of polypeptide chain from which projects the flexible substrate binding loop unique to chloride-dependent alpha-amylases. This structural feature also serves to properly orient the catalytically essential residue D300. Comparative analyses show that the chloride-independent alpha-amylases compensate for the absence of bound chloride by substituting a hydrophobic core, altering the manner in which substrate interactions are made and shifting the placement of N298. These evolutionary differences presumably arise in response to alternative operating environments or the advantage gained in a particular product profile. Attempts to engineer chloride-dependence into the chloride-independent TAKA-amylase point out the complexity of this system, and the fact that a multitude of factors play a role in binding chloride ion in the chloride-dependent alpha-amylases.
The line below this paragraph, {{ABSTRACT_PUBMED_15722449}}, adds the Publication Abstract to the page
(as it appears on PubMed at http://www.pubmed.gov), where 15722449 is the PubMed ID number.
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 15:00:57 2008''
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 21:13:07 2008''
Revision as of 21:13, 27 July 2008
This article has been automatically seeded. Changes to this page should pertain to the PDB entry only and not to the protein or biomolecule in general.
Structure of the N298S variant of human pancreatic alpha-amylase complexed with acarboseStructure of the N298S variant of human pancreatic alpha-amylase complexed with acarbose
1XH0 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Structural and mechanistic studies of chloride induced activation of human pancreatic alpha-amylase., Maurus R, Begum A, Kuo HH, Racaza A, Numao S, Andersen C, Tams JW, Vind J, Overall CM, Withers SG, Brayer GD, Protein Sci. 2005 Mar;14(3):743-55. PMID:15722449
