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Figure 1.
Figure 1 MDC architecture. (A) VAP1 dimer viewed from the NCS
axis. The H0-helix, M-domain, linker, D[s]-, D[a]-, C[w]-, and
C[h]-domains and HVRs belonging to the one monomer are shown in
red, yellow, gray, cyan, pink, gray, green and blue,
respectively. The disulfide-linked counterpart is shown in gray.
Zinc and calcium ions are represented as red and black spheres,
respectively. The NAG (N-acetyl-glucosamine, in orange) moieties
linked to Asn218, the calcium-mimetic Lys202 and the bound
inhibitor GM6001 (GM, in green) are in ball-stick
representations. (B) Stereo view of VAP1 monomer from the
direction nearly perpendicular to (A). The helix numbers are
labelled. (C) Superposition of the M-domains of ADAM33 (blue)
and VAP1 (yellow). The calcium ion bound to site I and the zinc
ion in ADAM33 are represented by black and red spheres,
respectively. The disulfide bridges are indicated in black and
blue letters for VAP1 and ADAM33, respectively. The QDHSK
sequence for the dimer interface in VAP1 (residues 320–324) is
in red. (D) Comparison of the calcium-binding site I structures
of ADAM33 (blue) and VAP1 (yellow) in stereo. The residues in
ADAM33 and in VAP1 are labelled in blue and black, respectively.
A calcium ion and a water molecule bound to ADAM33 are
represented as green and red spheres, respectively. The ammonium
group of Lys202 in VAP1 occupies the position of the calcium ion
in ADAM33. In ADAM33 (Orth et al, 2004), side-chain oxygen atoms
of Glu213, Asp296 and Asn407, the carbonyl oxygen of Cys404 and
a water molecule form the corners of a pentagonal bipyramid and
ligand to the calcium ion.
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