Figure 6.
Figure 6. a, The location and environment of the Ala 177 that
corresponds to the site of the A arrow
V polymorphism in human MTHFR. The view is approximately
perpendicular to the barrel axis and oriented to show helix 5
and its neighboring barrel strands. Black dot surfaces trace the
helix backbone from 171 to 176; red surfaces represent the
volume of alanine at position 177, and green surfaces a valine
substituted at position 177 which clearly overlaps the helix
backbone. The side chains of Lys 172, Asn 168, and Asp 165 that
interact with FAD are drawn in ball-and-stick mode with carbons
in cyan. b, The tetramer of E. coli MTHFR, viewed down the local
two-fold axis. The asymmetric unit of the monoclinic cell
contains the three chains A, B, and C; the fourth chain of the
tetramer (A') is related to A by a crystallographic two-fold
axis. The C and B subunits can be superimposed on chains A and
A' by a local dyad (perpendicular to the page) that is inclined
by ~53° to the crystallographic dyad along axis y. This
local dyad is the only symmetry operator that relates the chains
of the tetramer to one another. Interfaces A−A' and B−C are
formed by symmetric interactions between helices 7c,
7b,
and 8.
In contrast, the A and B (or C and A') chains are not related by
a simple rotation of 360/n^O; the B chain is superimposed on the
A chain by a rotation of 108° and a translation of ~7
Å. Helix 5, which may be critical in mediating the effects
of mutation at position 177, is drawn in red, and Ala 177 is
white and surrounded by dot surfaces. The figure was prepared
using the program RIBBONS^37.
The above figure is reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Biol
(1999,
6,
359-365)
copyright 1999.
arrow
V polymorphism in human MTHFR. The view is approximately
perpendicular to the barrel axis and oriented to show helix 
5
and its neighboring barrel strands. Black dot surfaces trace the
helix backbone from 171 to 176; red surfaces represent the
volume of alanine at position 177, and green surfaces a valine
substituted at position 177 which clearly overlaps the helix
backbone. The side chains of Lys 172, Asn 168, and Asp 165 that
interact with FAD are drawn in ball-and-stick mode with carbons
in cyan. b, The tetramer of E. coli MTHFR, viewed down the local
two-fold axis. The asymmetric unit of the monoclinic cell
contains the three chains A, B, and C; the fourth chain of the
tetramer (A') is related to A by a crystallographic two-fold
axis. The C and B subunits can be superimposed on chains A and
A' by a local dyad (perpendicular to the page) that is inclined
by ~53° to the crystallographic dyad along axis y. This
local dyad is the only symmetry operator that relates the chains
of the tetramer to one another. Interfaces A−A' and B−C are
formed by symmetric interactions between helices