title: Structural analysis of free and enzyme-bound amaranth alpha-amylase inhibitor: classification within the knottin fold superfamily and analysis of its functional flexibility.
abstract: The three-dimensional structure of the amaranth alpha-amylase inhibitor (AAI) adopts a knottin fold of abcabc topology. Upon binding to alpha-amylase, it adopts a more compact conformation characterized by an increased number of intramolecular hydrogen bonds, a decreased volume and in addition a trans to cis isomerization of Pro20. A systematic analysis of the 3-D structural databanks revealed that similar proteins and domains share with AAI the characteristic presence of proline residues, many of which are in a cis backbone conformation. As these proteins fulfil a variety of functional roles and are expressed in very different organisms, we conclude that the structure of the knottin fold, including the propensity of the cis bond, are the result of convergent evolution.
authors.affiliation: International Centre for Genetic Engineering and Biotechnology, Padriciano 99, Trieste Department of General Chemistry, University of Pavia, Pavia, Italy.
authors.forename: O
authors.initials: O
authors.lastname: Carugo
authors.forename: S
authors.initials: S
authors.lastname: Lu
authors.forename: J
authors.initials: J
authors.lastname: Luo
authors.forename: X
authors.initials: X
authors.lastname: Gu
authors.forename: S
authors.initials: S
authors.lastname: Liang
authors.forename: S
authors.initials: S
authors.lastname: Strobl
authors.forename: S
authors.initials: S
authors.lastname: Pongor
mesh_terms: D000465:Algorithms; D027721:Amaranthus / Q000201:enzymology*; D001665:Binding Sites; D005075:Biological Evolution; D016000:Cluster Analysis; D003553:Cystine / Q000737:chemistry*; D030562:Databases, Protein; D004220:Disulfides / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism*; D006860:Hydrogen Bonding; D008958:Models, Molecular; D010940:Plant Proteins / Q000737:chemistry* / Q000145:classification / Q000378:metabolism* / Q000502:physiology; D011392:Proline / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D012639:Seeds / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014361:Trypsin Inhibitors; D000516:alpha-Amylases / Q000037:antagonists & inhibitors / Q000145:classification / Q000378:metabolism*
chemical_list: D004220:Disulfides; D004791:Enzyme Inhibitors; D010940:Plant Proteins; D014361:Trypsin Inhibitors; D003553:Cystine; D011392:Proline; D000516:alpha-Amylases