Protein Modeling C

[Phenylethylamine]

He has XLP (X-linked lymphoproliferative disorder). I think about one in a million males (females can't get it, because they have two X chromosomes) have it, so it's rare, but not so rare it doesn't have a name.

Note that not all cases of XLP are caused by XIAP deficiency. More than half (~60%) are caused by a mutation in a completely different protein. While roughly one in a million males are predicted to have the disease, there have only been about 400 cases reported (ever). The "chronic hemorrhagic colitis" (the bowel problems that Nic had) seems to be unique to the XIAP type of XLP (XLP-2), though.

[gsheni]

What about finding specific residues for PARP1, the on site model for states?
I have looked in google scholar and have come up empty.

[Phenylethylamine]

What about finding specific residues for PARP1, the on site model for states?
I have looked in google scholar and have come up empty.

Try downloading 3OD8.pdb and looking at it in Jmol, with sidechains on ("select protein and sidechain"; "wireframe 200"). If you know the function of PARP (and there's some information about it in the Protein Modeling/Apoptosis Wiki), you may be able to come up with a few residues that appear to be important, based on the position of their sidechains.

[Helicase]

I want to do some creative additions to the Pre-build besides XIAP (chain c), but I can't really think of any. Would the connection (wherever that is) between chain a and b be a creative addition? Or what about the numbers on the number map http://cbm.msoe.edu/includes/jmol/SOJmo ... berMap.pdf
here? The numbers on the chart are different than the numbers on http://www.pdb.org/pdb/explore/remediat ... sPerPage=3
so would they be creative additions?
Also- where can i find reliable information on caspase-3 besides wiki? Sorry for all of the questions, help would be appreciated!

[Helicase]

I want to do some creative additions to the Pre-build besides XIAP (chain c), but I can't really think of any. Would the connection (wherever that is) between chain a and b be a creative addition? Or what about the numbers on the number map http://cbm.msoe.edu/includes/jmol/SOJmo ... berMap.pdf
here? The numbers on the chart are different than the numbers on http://www.pdb.org/pdb/explore/remediat ... sPerPage=3
so would they be creative additions?
Also- where can i find reliable information on caspase-3 besides wiki? Sorry for all of the questions, help would be appreciated!

sorry i just realized that the numbers are indeed the same- but would including them on the build and included on the card be an addition?

[Phenylethylamine]

I want to do some creative additions to the Pre-build besides XIAP (chain c), but I can't really think of any. Would the connection (wherever that is) between chain a and b be a creative addition? Or what about the numbers on the number map http://cbm.msoe.edu/includes/jmol/SOJmo ... berMap.pdf
here? The numbers on the chart are different than the numbers on http://www.pdb.org/pdb/explore/remediat ... sPerPage=3
so would they be creative additions?
Also- where can i find reliable information on caspase-3 besides wiki? Sorry for all of the questions, help would be appreciated!

sorry i just realized that the numbers are indeed the same- but would including them on the build and included on the card be an addition?

No, I don't believe that would constitute a creative addition on its own, unless you found some way to show the numbering that highlighted its involvement in how the protein's structure relates to its function (e.g., if you showed which sections were added/deleted relative to caspase-1, which is what the numbering is based on, and somehow connected that to how the addition/removal of those sections is specific to the function of caspase-3).

As far as resources, I recommend, as always, Wikipedia, the CBM site, the 1I3O primary citation, Google Scholar, and the PDB, especially the Molecule of the Month page.

[pawsup]

Hi,
I am having problems determining what is going on with the PARP inactivation. I understand Caspase-3 is responsible for cleaving PARP, and according to Wikipedia's page on PARP ( http://en.wikipedia.org/wiki/Poly_ADP_ribose_polymerase ), "cleavage occurs at aspartic acid 214 and glycine 215, separating PARP into a 24kDA and 89kDA segment." But on the 3od8.pdb file the chains shown are numbered amino acids 5-91. So is the 3od8.pdb missing this chain? or where does the cleavage actually occur?
Thanks in advance.

[Phenylethylamine]

Hi,
I am having problems determining what is going on with the PARP inactivation. I understand Caspase-3 is responsible for cleaving PARP, and according to Wikipedia's page on PARP ( http://en.wikipedia.org/wiki/Poly_ADP_ribose_polymerase ), "cleavage occurs at aspartic acid 214 and glycine 215, separating PARP into a 24kDA and 89kDA segment." But on the 3od8.pdb file the chains shown are numbered amino acids 5-91. So is the 3od8.pdb missing this chain? or where does the cleavage actually occur?
Thanks in advance.

3OD8 is just a very small piece of PARP, which is overall a much, much larger protein. Cleavage of PARP occurs at a point that isn't actually in this crystal structure (like you said, between residues 214 and 215); we only have a small portion of what ends up being the 24 kDa segment here (actually, we have a bunch of copies of it, but they're all identical).

So yes, 3OD8.pdb is "missing" the rest of the protein, but that's because it's a structure specifically of this bit of the DNA-binding domain of PARP, which they must want us to focus on for some reason.

[pawsup]

Thanks....I was going to try to add PARP to my pre-build to show the caspase-3 in action. Do you know where I might find a jmol of the whole PARP? or at least the section where it is cleaved?
Also, I understand the pink helices are alpha helices, but what is the dark purple/pink structures? Is that a different type of helix?

Thanks again!

[butter side up]

Thanks....I was going to try to add PARP to my pre-build to show the caspase-3 in action. Do you know where I might find a jmol of the whole PARP? or at least the section where it is cleaved?
Also, I understand the pink helices are alpha helices, but what is the dark purple/pink structures? Is that a different type of helix?

Thanks again!

The purple helices are 3 10 helices. (10 should be subscripted) They are slightly tighter than the normal alpha helices, about 3 amino acids per turn, as opposed to 3.6 in a normal alpha helix.

Edit: Thanks for catching my error, Phenylethylamine!

[Phenylethylamine]

Thanks....I was going to try to add PARP to my pre-build to show the caspase-3 in action. Do you know where I might find a jmol of the whole PARP? or at least the section where it is cleaved?

You're unlikely to find any crystal structure for the whole protein: it's roughly 110 kDa altogether (for perspective, both chains of caspase-3 combined are a bit under 30 kDa), so it's really quite large.

To find structures for other parts of PARP (although I can't guarantee that anyone's published a structure that includes the particular spot where it's cleaved, but you can look, there might well be one), search the PDB for "PARP" or its full name, "poly(ADP-ribose) polymerase". You'll get a whole bunch of results, many of which won't be relevant, but for any results that are actually parts of PARP, you can go to their sequence summary page and see if they include amino acids 214 and 215.

Thanks....I was going to try to add PARP to my pre-build to show the caspase-3 in action. Do you know where I might find a jmol of the whole PARP? or at least the section where it is cleaved?
Also, I understand the pink helices are alpha helices, but what is the dark purple/pink structures? Is that a different type of helix?

Thanks again!

The purple helices are 3 10 helices. (10 should be subscripted) They are slightly tighter than the normal alpha helices, about 3 amino acids per turn, as opposed to 3.4 in a normal alpha helix.

An alpha helix has 3.6 residues per turn, but otherwise, this is correct.

Also note that in the online competition environment (whether we're talking about the prebuild one or the onsite ones we'll have in competition), an older version of Jmol is used, in which 3/10 helices appear the same color as regular alpha helices. If I had to guess, I'd say this also means that they're unlikely to ask you anything about 3/10 helices in competition, or take points off for folding them as if they were alpha helices (which is not to say that you shouldn't strive for maximum accuracy whenever possible).

[gsheni]

Why does Chain F of XIAP
http://www.pdb.org/pdb/explore/remediat ... all&page=2
Have a huge gap from 169 - 179 ?
what can i do about it if I am modeling that chain?

[TheWiseGirl]

Does anybody know what a linker peptide is? I can't seem to find a straightforward explanation on google...

[Phenylethylamine]

Why does Chain F of XIAP
http://www.pdb.org/pdb/explore/remediat ... all&page=2
Have a huge gap from 169 - 179 ?
what can i do about it if I am modeling that chain?

The gap is just an area that they couldn't resolve properly in the x-ray crystallography. Model chain F based on the structure of chain E – they're identical.

Does anybody know what a linker peptide is? I can't seem to find a straightforward explanation on google...

The reason you can't find a straightforward explanation is because it's not a specific thing – it's a pretty general phrase. It's just being used to mean a peptide (as in a series of amino acids, in this case part of a protein) that links two sections of the protein.

[dolphin0922]

Is the side chain Asp175 significant? It seems like it becomes activated if this is cleaved, but I am not sure.