1. Volume 44, Issue 6, Pages 997-1004 (December 2011)
Mechanism of Isoprenylcysteine Carboxyl Methylation from the Crystal Structure of the Integral Membrane Methyltransferase ICMT 
Jing Yang, Kiran Kulkarni, Ioannis Manolaridis, Ziguo Zhang, Roger B. Dodd, Corine Mas-Droux, David Barford 
Molecular Cell 
Volume 44, Issue 6, Pages (December 2011)
DOI: /j.molcel
Copyright © 2011 Elsevier Inc. Terms and Conditions

2. Figure 1
Ma-ICMT Is an Integral Membrane Protein with Five α Transmembrane Helices and a C-Terminal Cytoplasmic α Helix
Two views of ICMT showing the L3 loop in red and conserved motifs M1 (125RHPxY) and M2 (163R[x]3EE) in yellow. The membrane is indicated by the gray background, based on the distribution of nonpolar residues and transmembrane helix predictions. The cofactor-binding pocket resides in the cytosol. Inner cavities are displayed in red, showing that the SAH-binding pocket matches the closed conformation of the cofactor and is linked to the lipid substrate access tunnel. See also Figures S1–S3.
Molecular Cell  , DOI: ( /j.molcel )
Copyright © 2011 Elsevier Inc. Terms and Conditions

3. Figure 2
Cofactor Is Completely Enclosed by Conserved Regions of Ma-ICMT
(A) Details of interactions of the SAH amino group with the M1 (125RHP[x]Y) and M2 (163R[x]3EE) motifs. The cofactor-binding cavity (volume of 1291 Å3) is generated from the L3 loop and cytosolic segment of H5 and H6. View as in Figure 1 (left). The Tyr129 side chain is omitted for clarity.
(B) Rotated view showing cofactor-binding residues, highlighting nonpolar contacts with the cofactor adenine ring. The Arg125 side chain is omitted for clarity.
(C) Sequence alignment of conserved C-terminal catalytic subdomain. Residues mutated in this study and which disrupt activity are indicated in blue with S. cerevisiae ICMT numbering in parenthesis. Substituted residues indicated in black (104 and 171) inactivate S. cerevisiae ICMT (Romano and Michaelis, 2001).
See also Figures S1–S3.
Molecular Cell  , DOI: ( /j.molcel )
Copyright © 2011 Elsevier Inc. Terms and Conditions

4. Figure 3
The Buried Cofactor Pocket Is Linked to the Inner Membrane and Cytosol by a Substrate Access Tunnel
(A) Surface representation of Ma-ICMT with SAM (modeled on SAH) and AFC occupying the substrate tunnel. The membrane is indicated by two horizontal dashed lines.
(B) Cross-section of Ma-ICMT. The upper hydrophobic region of the substrate-tunnel provides access for prenylated lipid from the inner membrane, whereas the lower polar region of the tunnel accommodates the polar C terminus of the prenylated protein.
(C) Model of AFC bound to the substrate access tunnel. The carboxylate of AFC is proximal to the guanidinium group of Arg163 and in direct line of attack of the reactive methyl group (purple) of SAM.
(D) Schematic of S-farnesylated protein bound to ICMT.
Molecular Cell  , DOI: ( /j.molcel )
Copyright © 2011 Elsevier Inc. Terms and Conditions

5. Figure 4
Mutation of Cofactor and Putative Substrate-Binding Residues Impairs Ma-ICMT and Sc-ICMT Methyltransferase Activity
(A) Specific activity of wild-type and mutant yeast ICMT toward AFC. Sc-ICMT, S. cerevisiae ICMT; MP, membrane protein control (membrane without overexpression of ICMT). The specific activity is comparable to published data (Anderson et al., 2005).
(B) Specific activity of wild-type and mutant Ma-ICMT toward FTA.
(C) Ma-ICMT has measurable activity toward AFC, compared with mutant Ma-ICMT (E167A) and membrane control (MP).
In all panels of this figure, error bars denote one standard deviation, n = 3. Specific activities were determined as described (Griggs et al., 2010). See also Figure S4.
Molecular Cell  , DOI: ( /j.molcel )
Copyright © 2011 Elsevier Inc. Terms and Conditions