1y1b
From Proteopedia
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Solution structure of Anemonia elastase inhibitor
Overview
Anemonia elastase inhibitor (AEI) is a "nonclassical" Kazal-type elastase, inhibitor from Anemonia sulcata. Unlike many nonclassical inhibitors, AEI, does not have a cystine-stabilized alpha-helical (CSH) motif in the, sequence. We chemically synthesized AEI and determined its, three-dimensional solution structure by two-dimensional NMR spectroscopy., The resulting structure of AEI was characterized by a central alpha-helix, and a three-stranded antiparallel beta-sheet of a typical Kazal-type, inhibitor such as silver pheasant ovomucoid third domain (OMSVP3), even, though the first and fifth half-cystine residues forming a disulfide bond, in AEI are shifted both toward the C-terminus in comparison with those of, OMSVP3. Synthesized AEI exhibited unexpected strong inhibition toward, Streptomyces griseus protease B (SGPB). Our previous study [Hemmi, H., et, al. (2003) Biochemistry 42, 2524-2534] demonstrated that the site-specific, introduction of the engineered disulfide bond into the OMSVP3 molecule to, form the CSH motif could produce an inhibitor with a narrower specificity., Thus, the CSH motif-containing derivative of AEI (AEI analogue) was, chemically synthesized when a Cys(4)-Cys(34) bond was changed to a, Cys(6)-Cys(31) bond. The AEI analogue scarcely inhibited porcine, pancreatic elastase (PPE), even though it exhibited almost the same potent, inhibitory activity toward SGPB. For the molecular scaffold, essentially, no structural difference was detected between the two, but the N-terminal, loop from Pro(5) to Ile(7) near the putative reactive site, (Met(10)-Gln(11)) in the analogue moved by 3.7 A toward the central helix, to form the introduced Cys(6)-Cys(31) bond. Such a conformational change, in the restricted region correlates with the specificity change of the, inhibitor.
About this Structure
1Y1B is a Single protein structure of sequence from [1]. Full crystallographic information is available from OCA.
Reference
Structural and functional study of an Anemonia elastase inhibitor, a "nonclassical" Kazal-type inhibitor from Anemonia sulcata., Hemmi H, Kumazaki T, Yoshizawa-Kumagaye K, Nishiuchi Y, Yoshida T, Ohkubo T, Kobayashi Y, Biochemistry. 2005 Jul 19;44(28):9626-36. PMID:16008348
Page seeded by OCA on Wed Nov 21 06:29:25 2007
