3D structure

There are several ways of seeing if there is a known 3D structure of this protein. There are links from UniProtKB/Swiss-Prot and the other databases to a number of PDB entries including 3ecr, the structure of human porphobilinogen deaminase at 2.18Â resolution.

However it is often the case that the structure of a protein of interest has not been solved and will not be available in the Protein Databank. If that is the case, we can build a homology model, but we can also take a simpler approach.

If there is a structure for a closely related protein (e.g. the same protein - orthologue - from another species), then one can simply inherit information from that other species by aligning the sequences and copying across structural annotations from the known structure to the sequence of interest.

One of the better ways of doing this is to use the SAS database (which stands for Sequences Annotated by Structure).

Let's suppose we are interested in the structure of the second hit that you obtained when you performed the BLAST search. There is no solved structure solved (although models are available). Here is its sequence:

MSGNGNAAAIAEEDTPKMRVIRVGTRKSQLARIQTDSVVATLKALYPGLQFEIIAMSTTG
DKILDTALSKIGEKSLFTKELEHALERNEVDLVVHSLKDLPTVLPPGFTIGAVCKRESPY
DAVVFHPKFVGKTLETLPEKSVVGTSSLRRAAQLQRKFPHLEFKSIRGNLNTRLRKLDEL
QEFSAIILATAGLQRMGWQNRVGQILHPEECMYAVGQGALGVEVRAKDQDILDLVGVLHD
PETLLRCIAERSFLRHLEGGCSVPVAVHTAIKDGQLYLTGGVWSLNGAETMQDTMQTTIH
VPVQHEDGPEDDPQLVGITARNIPRQPQLAAENLGISLATLLLNKGAKNILDVARQLNEA
H

1. Go to the SAS
2. Under c. Pasted sequence, paste the protein sequence above into the large box.
3. Click Search

This will show you which 3D structures in the PDB database give the best sequence-matches to your sequence. Their sequence identities to the mystery protein are given towards the end of the page.

Near the top of the page, the sequence is displayed beneath a secondary structure annotation which is taken from the closest homologue for which a structure is known. You will note the following:

• Some residues have a red box around them indicating they are listed as catalytic site residues in the Catalytic Site Atlas
• Some residues have a coloured triangle above them. These represent structural annotations from the crystal structure(s) such as active sites, contact residues, etc. Clicking a triangle will open a window explaining these annotations.
• Some residues have a small coloured rectangle below them. These indicate matches to ProSite patterns with the colour representing the degree of conservation of these postions.

In the sequence alignment, residues annotated in the main display will be shown in colour. When only some of the entries in a column are shown in colour, this indicates that only some PDB files have annotations.

When there are molecules bound to the proteins in the 3D structures, it is important to understand what they are doing. Clicking on the PDB code in the multiple alignment will take you to the PDBsum page for that structure and there you can find out what any bound molecules are. If they are described as cofactors then they are "helper" molecules that enable the protein to perform its enzymatic function. They are not the protein's substrate molecules - i.e. molecules on which the enzyme performs its function - but merely assistants.