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Figure 6
Comparison of the AHNAK–S100A10–AnxA2 binding interface with other S100 proteins. (a) Superposition of S100A4–myosin IIA (PDB entry 3zwh ) onto AHNAK–(p11)2(AnxA2)2 (r.m.s.d. 1.48 Å). Key differences between S100A10 (blue) and S100A4 (dark green) are thought to create steric clashes with the AHNAK peptide (yellow). Ala81 is substituted by Met85 in S100A4, resulting in a clash with Thr4 of AHNAK on chain A of S100A4 and with Phe13 of AHNAK on chain B. Additionally, the substitution of Gly77 by Ser81 in S100A4 (Cys81 in the native sequence) is predicted to result in a steric clash on both chains as the hydroxyl groups of serine comes into close contact with Pro6 and Ile10 (AHNAK). (b) Superposition of S100B–TRTK12 (PDB entry 3rm1 ) and AHNAK–(p11)2(AnxA2)2 (r.m.s.d. 1.49 Å). Although S100B is a known binding partner of AHNAK, the peptide which shows high affinity for S100A10–AnxA2 is not likely to be the same sequence that binds to the S100B dimer. Two mutations, Gly77 to Met79 and Ser73 to Ala75, cause steric clashes and a loss of hydrogen bonding between both chains of S100B (magenta) and the AHNAK peptide (yellow). (c) Superposition of S100A11–AnxA1 (PDB entry 1qls ) onto AHNAK–(p11)2(AnxA2)2 (r.m.s.d. 1.19 Å). The AHNAK binding surface on S100A10–AnxA2 shows high similarity to this surface on S100A11–AnxA1 (gray). The hydrogen bond between Gly1 of AHNAK (yellow) and Ser12 of AnxA2 (lime green) could be supplemented by a hydrogen bond to Trp11 of AnxA1 instead. Unlike S100A4 and S100B, which do not conserve Gly77 of S100A10, S100A11 retains this residue (Gly84) and no steric clashes are predicted to occur. The only notable change is Ser73 to Asn80, which disrupts hydrogen bonds between both chains of S100A11 and AHNAK. However, the side-chain amide of Asn80 could play the role of the side-chain hydroxyl of Ser73 and donate hydrogen bonds to main-chain atoms on AHNAK. Lower-case letters represent chain IDs.

Journal logoBIOLOGICAL
ISSN: 1399-0047
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