Difference between revisions of "Task 9: Structure-based mutation analysis"

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Lab_Journal_Hemochromatosis_Task9

Structure Selection

PDB ID	Res [A]	R-value (obs)	pH	missing residues	coverage
1A6Z	2.60	2.33	6.5	1-3	83.4%
1DE4	2.80	2.31	8.0	1-3	83.4%

From the two available structures, we chose 1A6Z, because it has a slightly higher resolution and a nearly identical resolution compared to 1DE4. On the downside, 1A6Z was resolved at a pH value of 6.5, which is more distant to the physiological pH than the resolution pH of 1DE4. 1A6Z was chosen nevertheless, because it was used in all previous tasks, in order to keep consistency.

Mutations

Mutation	Disease causing ?
Val53Met	Yes
His63Asp	Yes
Met97Ile	No
Thr217Ile	No
Cys282Tyr	Yes

</figtable>

Structure Mutation using SCWRL

Val53Met

**Figure 2:** Wild type(grey) and mutant(red) residues for position 53.

</figtable> Figure 2 shows that the mutation to Methionin does not change the polar contacts of the residue. But Methionin extends further into the binding pocket than Valin, which might disturb the structure of the binding pocket and inhibit the binding process.

His63Asp

**Figure 3:** Wild type(grey) and mutant(red) residues for position 63.

Met97Ile

**Figure 4:** Wild type(grey) and mutant(red) residues for position 97.

T217I

**Figure 5:** Wild type(grey) and mutant(red) residues for position 217.

C282Y

**Figure 6:** Wild type(grey) and mutant(red) residues for position 282. The disulfide bridge binding partner of C282 is shown in white.

Structure Mutation using foldX

**Figure 7:** Comparison between mutations performed by SCWRL(green) and foldx(cyan).