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Science 19 September 1997:
Vol. 277. no. 5333, pp. 1811 - 1815
DOI: 10.1126/science.277.5333.1811
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Reports

Structure and Function of a Squalene Cyclase

K. Ulrich Wendt, Karl Poralla, Georg E. Schulz *

The crystal structure of squalene-hopene cyclase from Alicyclobacillus acidocaldarius was determined at 2.9 angstrom resolution. The mechanism and sequence of this cyclase are closely related to those of 2,3-oxidosqualene cyclases that catalyze the cyclization step in cholesterol biosynthesis. The structure reveals a membrane protein with membrane-binding characteristics similar to those of prostaglandin-H2 synthase, the only other reported protein of this type. The active site of the enzyme is located in a large central cavity that is of suitable size to bind squalene in its required conformation and that is lined by aromatic residues. The structure supports a mechanism in which the acid starting the reaction by protonating a carbon-carbon double bond is an aspartate that is coupled to a histidine. Numerous surface alpha  helices are connected by characteristic QW-motifs (Q is glutamine and W is tryptophan) that tighten the protein structure, possibly for absorbing the reaction energy without structural damage.

K. U. Wendt and G. E. Schulz, Institut für Organische Chemie und Biochemie, Albertstrasse 21, D-79104 Freiburg im Breisgau, Germany.
K. Poralla, Biologisches Institut, Mikrobiologie/Biotechnologie, Auf der Morgenstelle 28, D-72076 Tübingen, Germany.
*   To whom correspondence should be addressed. E-mail: schulz{at}bio5.chemie.uni-freiburg.de

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