Canavan Disease: Task 04 - Structural Alignments

Dataset

To gain the dataset as desired first a reference sequence (2I3C) was chosen. Then the dataset was generated using this sequence fulfilling the required criteria. The full composition and additional information can be found in <xr id="dataset"> Table </xr>. <figtable id="dataset">

Dataset composition
PDB-id	Description	Criterium
2I3C	ASPA from Human	reference structure
2O4H	ASPA from Human with bound N-phosphonomethyl-L-aspartate	sequence identity 100% & bound active centre
2Q51	ASPA from Human (Ensemble refinement)	sequence identity 100% & unbound active centre
2GU2	ASPA from Rat	seq. identity >60%
2QJ8	ASPA family protein from mesorhizobium loti	sequence identity <30%
1AYE	Procarbooxypeptidase from Human	similar CATH classification for CAT
1BKJ	FMN Oxireductase from vibrio harveyi	similar CATH classification for CA
1BD0	Alanine racemase	similar CATH classification for C
1B3U	Regulatory domain of human PP2A	completely different CATH classification

Overview of the dataset composition for Task 04, containing a brief description of the the chosen structures. Sequence identity and CATH classification similarities with respect to reference sequence 2I3C.

</figtable>

Structural Alignment Exploration

Pymol

2O4H vs. 2I3C

2O4H was found via the sequence search tab for the reference sequence 2I3C. The structure was chosen due to the fact that it is contained in the 100% sequence identity cluster. Additionally it has a bound compound in the active center however it is not N-acetyl-L-aspartate, but N-Hydroxy(methyl)phosphoric-L-aspartate binding to the same active center.

Due to the fact that 2O4H and 2I3C have 100% sequence identity, the structural alignment via Pymol works very accurate. Both structures are within the bounds of the accuracy of X-ray crystallography the same. The RMSD between 2OH4 and 2I3C, calculated by the alignment process of Pymol is 0.341Å. As the measure for the divergence is smaller than possible to reach resulution of the structure they can be safely considered to be identical. The visual representation of the structural alignment is displayed in <xr id="2O4H_pymol">Figure </xr>. <figure id="2O4H_pymol">

Representation of 2OH4 aligned to 2I3C. Both structures are displayed as carton, 2OH4 in black, 2I3C in orange. The zinc atom at the active site is represented as gray sphere, and the N-Hydroxy(methyl)phosphoric-L-aspartate is represented as balls and sticks at the active site. With a calculated RMSD of 0.341Å both structures can be considered the same as the divergence is even lower than the possible resolution of the crystal structure.

</figure>

2Q51 vs 2I3C

<figure id="2Q51_pymol">

Representation of 2Q51 aligned to 2I3C. Both structures are displayed as carton, 2Q51 in blue, 2I3C in orange. The zinc atom at the active site is represented as gray sphere.

</figure>

2GU2 vs 2I3C

<figure id="2GU2_pymol">

Representation of 2GU2 aligned to 2I3C. Both structures are displayed as carton, 2GU2 in turquoise, 2I3C in orange. The zinc atom at the active site is represented as gray sphere.

</figure>

2QJ8 vs 2I3C

<figure id="2QJ8_pymol">

Representation of 2GU2 aligned to 2I3C. Both structures are displayed as carton, 2QJ8 in green, 2I3C in orange. The zinc atom at the active site is represented as gray sphere.

</figure>

Remaining Proteins

<figure id="Remaining_pymol">

a) 1AYE vs 2I3C

b) 1BKJ vs 2I3C

c) 1BD0 vs 2I3C

d) 1B3U vs 2I3C

Foo Bar

</figure>

Tasks

• Link to Task 01: Canavan Disease
• Link to Task 02: Alignments
• Link to Task 03: Sequence-based Predictions
• Link to Task 04: Structural Alignments
• Link to Task 05: Homology Modelling
• Link to Task 06: Protein Structure Prediction from Evolutionary Sequence Variation
• Link to Task 07: Researching SNPs
• Link to Task 08: Sequence-based Mutation Analysis
• Link to Task 09: Structure-based Mutation Analysis
• Link to Task 10: Normal Mode Analysis
• Link to Task 11: Molecular Dynamics Simulation