Posts Tagged Structural Biology

Caroline and Raphael Protein Image

2HSJ Protein Visualization: Platelet Activating Factor from Streptococcus pneumonia

We examined protein 2HSJ, a probable platelet activating factor from S. pneumonia using PyMOL visualization tools. 2HSJ is a little studied protein that functions in lipid metabolism and hydrolysis. Our measurements show protein dimensions of 104.4 Å by  66.3 Å  by 52.5 Å (as seen in Image 1). This protein has known ligand binding between amino acid residues ALA 161 and VAL 167 (shown hot pink in Image 2).   A Consurf homology comparison using BLAST shows conserved areas in the central parts of each chain. However, much of the external surface, including the known ligand binding area, is categorized as having “insufficient data.” Thus, no conclusions about active site location based on Consurf conserved regions can be draw.

Platelet Activating Factor

Measurements shown on the structure of a probable platelet activating factor of S. pneumonia.

Platelet Activating Factor

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Lipase Consurf

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ConSurf Imaging

We used Consurf to visually analyze the structural basis for our enzyme Integrase. Since Integrase is found in viruses and functions to cleave and repackage the viral DNA we were expecting much of it to be conserved, especially near the active site. Looking at both the A and B chains we found it was most conserved on the A- chain and our guess of the active site was right on key. This was a very useful tool. In the end we found that we can actually compare both the A and B chains and check out the structural basis as a whole which was highly conserved as we expected it to be.

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Aldo-keto reductase

So here is con surf run of aldo keto reductase, it looks pretty conserved.

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ConSurf

Using ConSurf we analyzed both A and B chains of integrase. Both chains showed significant amounts of conservation but there was one specific area on the A chain that was incredibly highly conserved.  Even though an integrase can act upon viruses, which change frequently and rapidly, it is able to achieve its desired result while, itself, maintaining relatively stable.

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Protein Images for Joanna and Maurico

The protein we chose to look at was insulin.  Insulin is a signalling hormone that indicates levels of sugar in the blood.  It is synthesized in the pancreas, and the distributed through the body to have an effect on  many systems.  Insulin is a relatively small molecule, measuring aproximately 25x16x18 angstroms.  As such, cells actually synthesized as a larger molecule, and 2 chains are cut off.  Insulin is a great molecule to use to study protein structure, because it has multiple chains held together by disulfide bonds.  This image shows an insulin monomer, the A and B chains are in different colors, and the three disulfide bonds are shown with yellow sticks.

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PyMOL and Integrase-Jessica/Sara

Integrase is an enzyme that splices viral DNA; it is well known in studies of HIV. Four copies of integrase will attach to viral DNA and create a larger structure called an  intasome. This structure has 2 subunits toward the middle which will provide the active site where  the DNA is cut and attached together. This is important because it allows the viral genome to become part of the cell, furthermore propagating the virus. In the pyMOL image attached, you can see this active site mentioned.

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Anastasia and Thomas’s Investigation of Prion Structural Simularities in Rabbits (3O79), Mice and Humans

Prions are a destructive family of proteins, due to a transformational (mis-folding) of a alpha helix to a beta sheet. The beta sheets only represent 3% of the proteins secondary structure (Fig. 1) This minor change in protein conformation is enough to turn a useful protein into a highly destructive stable force.



Figure 1. 56% helical (5 helices; 59 residues) 3% beta sheet (2 strands; 4 residues) of 3070 rabbit prion

Its amino acid sequence (95% match in sheep) as well as its 3-D structure ( 97% similarity to humans) is highly conserved through different species. What makes misfolding such a problem is its ability to perpetuate misfolding of the surrounding proteins. It has been found that rabbits have a helix capping motif the dramatically lowers the propensity of prion formation (Fig. 2)

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rabbit

Figure 2: Mouse vs Rabbit 3-D cartoon structure using Pymol

In conclusion prions have a highly conserved structure that is both minor yet destructive.

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Leptin Protein Views (Steve and Ann)

We decided on Leptin, a hormone involed with appetite suppression, because obesity is an increasing problem in affluent countries and we are in one. There is one disulfide bridge within this protein, and 4 alpha helices adjacent to each other with multiple leucine residues that are highly conserved (as verified by Consurf). Also, there is a random chain that is not highly conserved except for a tail region, potentially meaning that this tail region is important for the protein’s function.

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Lipase visualization- Tara and Stefan

Lipase is an enzyme that hydrolyzes lipids. The structure we looked at came from Gibberella zeae and was obtained by xray diffraction. This enzyme is crucial to G. zeae pathogenicity. It contains 319 residues and measured 94 by 129 angstroms. We created an image of the electrostatics and of the atoms.

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