Task 9 (MSUD)

Results

Lab journal

For this task we have chosen 5 mutations from HGMD and dbSNP. 2 of them are neutral mutations which do not have functional changes over the protein structure. Following are the 5 mutations:

Database	Accession_code	Mutation	Pathogenic
dbSNP	rs11549938	M82L	False
dbSNP	rs141086188	A222T	False
HGMD	CM045934	C264W	True
HGMD	CM062448	R346H	True
dbSNP	rs61736656	I361V	False

Visualization of mutant structures

The mutagen tool of PyMOL was used to introduce mutations to the protein structure. Mutations and their neighboring residues are visualized and shown in following figures.

• Visualization of mutations in BCKDHA (PDB: 2BFF, all residue positions refer to the reference sequence of BCKDHA)
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  Local environment of residue 82. Original methionine is replaced by leucine.

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  Local environment of residue 222. Original alanine is replaced by threonine.

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  Local environment of residue 264. Original cysteine is replaced by tryptophan. Clearly, the mutant residue tryptophan clashes with the binding site (Green) for ion binding.

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  Local environment of residue 346. Original arginine is replaced by histidine.

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  Local environment of residue 361. Original isoleucine is replaced by valine.