Protein Modeling C

[sci-man]

this is a wierd question..... but its been bugging me for awhile.

from what direction is the "right hand helix" determined from?
the blue cap? red cap?
b/c last year i was nailed tons of pts for wrong direction helices

[Agggron]

The chain starts at blue and ends at red, so as a general rule of thumb you'd want to look in that direction first. But I don't think there's a difference even if you look at a right-handed helix in the opposite direction.

[Phenylethylamine]

this is a wierd question..... but its been bugging me for awhile.

from what direction is the "right hand helix" determined from?
the blue cap? red cap?
b/c last year i was nailed tons of pts for wrong direction helices

A "right-handed helix" will appear right-handed regardless of which end you look at it from.

First, a common trick for telling whether a helix is right- or left-handed is to imagine it as a spiral staircase; if your right hand would be on the outside railing while going up this staircase, it is a right-handed helix, while if it would be your left hand on the outside, it is a left-handed helix (which, for the purposes of proteins, is bad).

Now imagine you are going up a spiral staircase, and your right hand is on the outside railing. If you turned around and started going down, your left hand would be on the outside railing, it's true. But imagine you have an evil twin for whom gravity works backwards, and your evil twin is walking on the bottom of the spiral staircase, going down (which, of course, they perceive as "up" because their gravity is reversed). If you think about a point where you're both at the same spot and facing the same direction, your twin has the opposite hand on the railing as you do – so as your twin goes down the bottom of the staircase (or "up", from their point of view), their right hand is also on the outside railing.

My point is, flipping a helix over (i.e., looking at it red-cap-to-blue-cap direction instead of blue-cap-to-red-cap direction) isn't like going down the spiral staircase instead of up; it's like looking at your evil twin's path instead of your own. Yes, you're going in the opposite direction, but you also changed which direction was up, so it's still the right hand on the outside railing, and thus a right-handed helix.

[Mithrandir]

So I brought up the mutation of CYS 285 to soinc.org. They said that the mutation is only there because it keeps the crystallization in a specific shape and to use CYS 285 our models.

03/01/2012 - 16:40 The 285 side chain says it is Alanine. However, it is according to the 1i3o pdb file found on the Protein data bank, it is mismatched to Cysteine in UniProtKB. It is key to the structure if the 285 side chain is Cysteine and not Alanine. Which do ...

The PDB file 1i3o has a mutation at Cys285 in which Alanine was used instead. The cysteine is indeed important to the function and this should be used in the model. The sequence information tells you that Cys should be in that position. The mutation was done to keep the enzyme in a particular conformation for the crystallization process. This information can be found in the primary citation associated with the PDB file.

http://soinc.org/node/289

[paronomasia]

How do we figure out what to do /what are you guys modeling for our add-ons? I know last year it was zinc ions and DNA but beyond the active sites for this year I can't find anything. I've searched the RCSB PDB and waded through scholarly articles and haven't found very much.

[Phenylethylamine]

How do we figure out what to do /what are you guys modeling for our add-ons? I know last year it was zinc ions and DNA but beyond the active sites for this year I can't find anything. I've searched the RCSB PDB and waded through scholarly articles and haven't found very much.

Try thinking about ways to show the role of caspase-3 in the apoptosis cascade. What substrates does it cleave? What happens to the cell when it does that? How is caspase-3 activated? How is caspase-3 prevented from just breaking down the cell all the time (e.g., what inhibits it, what is its inactive form)?

These questions are a good place to start with your creative additions, but overall, your goal is to tell the "molecular story" of caspase-3, so anything that helps elucidate the connection between structure and function of this protein is good.

I'm a little wary of posting specific creative additions on the forums, because they are intended to be, as the name suggests, creative. They're the part of the event where each team puts in their own interpretation. If you study caspase-3 and XIAP to the point that you really understand their functions and how each part of the protein contributes to exactly what it does, not only will you have many great ideas for how to show those functions as creative additions, but you'll also be in great shape for the test in competition.

[TheWiseGirl]

@Phenyl: I just took your practice test, and while it did lean towards the easy side, it was still VERY nicely written. You'll go on to write great tests for Science Olympiad!

[Phenylethylamine]

@Phenyl: I just took your practice test, and while it did lean towards the easy side, it was still VERY nicely written. You'll go on to write great tests for Science Olympiad!

Thanks! It was written as a placement test of sorts to determine who would be doing the event on some of our B teams, so many of the people taking it had just recently picked up the event. I tried to keep it at a reasonable level for them; I didn't want to go from having four people on one team want to do Protein to suddenly having none.

Also, writing this test was the first major thing I did for this event this year, what with college apps and all, so my own knowledge of this year's specifics at the time was relatively limited. I do find that writing practice tests is a pretty good way to study, so I may write another sometime in the next month (if I have time) and post it.

[soccer_5456]

@Phenyl: I just took your practice test, and while it did lean towards the easy side, it was still VERY nicely written. You'll go on to write great tests for Science Olympiad!

I agree!!

I have a question about PARP. After doing research, I became confused over how the apoptosis cascade continues with PARP. What exactly happens? Is it the overactivation of PARP (after Caspase-3 cleavage at the specific domain) which causes PARP to use all the NAD+ in the cell with PAR systhesis and then ATP depletion in the cell? Or is it the inactivation of PARP after Caspase-3 cuts the DNA-binding domain from the essential catalytic domain and the auto-modification domain, causing the DNA-binding domain to clog up the SSB?

Aren't these two processes very different? Or do they work in conjunction?

[soccer_5456]

Also, do cytochrome-c and ATP interact with pro-caspase-9 BEFORE XIAP inhibits caspase-9? Can XIAP even "inhibit" a zymogen?..