1iac
From Proteopedia
|
REFINED 1.8 ANGSTROMS X-RAY CRYSTAL STRUCTURE OF ASTACIN, A ZINC-ENDOPEPTIDASE FROM THE CRAYFISH ASTACUS ASTACUS L. STRUCTURE DETERMINATION, REFINEMENT, MOLECULAR STRUCTURE AND COMPARISON WITH THERMOLYSIN
Overview
Astacin, a 200 residue digestive zinc-endopeptidase from the crayfish, Astacus astacus L., is the prototype of the "astacin family", which, comprises several membrane-bound mammalian endopeptidases and, developmentally implicated regulatory proteins. Large trigonal crystals of, astacin were grown, and X-ray reflection data to 1.8 A resolution were, collected. The astacin structure has been solved by multiple isomorphous, replacement using six heavy-atom derivatives, and refined to a, crystallographic R-value of 0.158 applying stringent constraints. All 200, residues are clearly defined by electron density; 181 solvent molecules, have been localized. Besides the native structure, the structures of, Hg-astacin (with a mercury ion replacing the zinc) and of the apoenzyme, were also refined. The astacin molecule exhibits a kidney-like shape. It, consists of an amino-terminal and a carboxy-terminal domain, with a deep, active-site cleft in between. The zinc ion, located at the bottom of this, cleft, is co-ordinated in a novel trigonal-bipyramidal geometry by three, histidine residues, a tyrosine and by a water molecule, which is also, bound to the carboxylate side-chain of Glu93. The amino-terminal domain of, astacin consists mainly of two long alpha-helices, one centrally located, and one more peripheral, and of a five-stranded pleated beta-sheet. The, amino terminus protrudes into an internal, water-filled cavity of the, lower domain and forms a buried salt bridge with Glu103; amino-terminally, extended pro-forms of astacin are thus not compatible with this structure., The carboxy-terminal domain of astacin is mainly organized in several, turns and irregular structures. Because they share sequence identity of, about 35%, the structures of the proteolytic domains of the other, "astacin" members must be quite similar to astacin. Only a few very short, deletions and insertions quite distant from the active-site distinguish, their structures from astacin. The five-stranded beta-sheet and the two, helices of the amino-terminal domain of astacin are topologically similar, to the structure observed in the archetypal zinc-endopeptidase, thermolysin; the rest of the structures are, in contrast, completely, unrelated in astacin and thermolysin. The zinc ion, the central, alpha-helix and the zinc-liganding residues His92, Glu93 and His96 of, astacin are nearly superimposable with the respective groups of, thermolysin, namely with the zinc ion, the "active-site helix", and, His142TL, Glu143TL and His146TL of the zinc-binding consensus motif, His-Glu-Xaa-Xaa-His (where Xaa is any amino acid residue).(ABSTRACT, TRUNCATED AT 400 WORDS)
About this Structure
1IAC is a Single protein structure of sequence from Astacus astacus with HG as ligand. Active as Astacin, with EC number 3.4.24.21 Full crystallographic information is available from OCA.
Reference
Refined 1.8 A X-ray crystal structure of astacin, a zinc-endopeptidase from the crayfish Astacus astacus L. Structure determination, refinement, molecular structure and comparison with thermolysin., Gomis-Ruth FX, Stocker W, Huber R, Zwilling R, Bode W, J Mol Biol. 1993 Feb 20;229(4):945-68. PMID:8445658
Page seeded by OCA on Tue Nov 20 17:12:55 2007
