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PDBsum entry 1sqc
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References listed in PDB file
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Key reference
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Title
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Structure and function of a squalene cyclase.
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Authors
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K.U.Wendt,
K.Poralla,
G.E.Schulz.
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Ref.
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Science, 1997,
277,
1811-1815.
[DOI no: ]
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PubMed id
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Abstract
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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.
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Figure 1.
Fig. 1. The proposed reaction steps in squalene-hopene
cyclases involving carbocationic intermediates. The general acid
B[1]:H protonates (H) squalene at C3, whereas the general base
B[2] deprotonates at C29 of the hopenyl cation. In a side
reaction, the cation is hydroxylated^ forming hopan-22-ol.
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Figure 5.
Fig. 5. The color-coded surface representations (30) with
nonpolar (yellow), positive (blue), and negative (red) areas.
(A) View similar to Fig. 2 but rotated around a vertical axis
and^ sliced. The cutting plane (checked) opens the large
internal cavity with the bound inhibitor LDAO. The nonpolar
channel runs to the^ left, opening into a nonpolar plateau. The
channel constriction (C) appears closed, but it is mobile enough
to be readily opened. At the upper left, hopane (two views) is
shown at scale. (B) View similar to Fig. 2 directly onto the
1600 Å2 nonpolar plateau with the channel entrance (E) at
its center and two nonpolar side chains pointing to the outside.
This is the only large nonpolar region on the surface.
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The above figures are
reprinted
by permission from the AAAs:
Science
(1997,
277,
1811-1815)
copyright 1997.
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Secondary reference #1
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Title
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Crystallization and preliminary X-Ray crystallographic analysis of squalene-Hopene cyclase from alicyclobacillus acidocaldarius.
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Authors
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K.U.Wendt,
C.Feil,
A.Lenhart,
K.Poralla,
G.E.Schulz.
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Ref.
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Protein Sci, 1997,
6,
722-724.
[DOI no: ]
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PubMed id
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