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1443: Classroom Puzzle: Engineer the Active Site
Status: Closed

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toshiue's picture
User offline. Last seen 1 week 1 day ago. Offline
Joined: 01/31/2016
Groups: Go Science
The two papers by Lau and Lameira

I don't have, and I imagine most don't have enough credentials to download the PDFs of those two papers. Is it possible for someone with enough credentials to DL both PDFs and post in the Forum for us to read? Thanks...

dbuske's picture
User offline. Last seen 16 hours 29 min ago. Offline
Joined: 09/22/2011
Groups: Beta Folders
Bridges

Alot of bridges with this one!
Will disulfide bridges form and fold in this puzzle?

LociOiling's picture
User offline. Last seen 2 hours 17 min ago. Offline
Joined: 12/27/2012
Groups: Beta Folders
sorry, looks like no bridges

The puzzle has 17 cysteines, but there are also 3 mystery atoms floating around, segments 250 to 252. It looks like they're zinc atoms, held in place by nearby cysteines. (There's also a small molecule at 249.)

PDB entry 5V22 is one example of this protein. You can find it at rcsb.org. The segment numbers are different, but the amino acids are a match. It indicates the individual atoms are zincs.

In our protein, the zincs at 250 and 251 are near each other, and they've held in place by cysteines 56, 58, 73, 77, 86, 90, and 96, if I've got this right.

The zinc at 252 is held by cysteines 188, 235, 237, and 242.

So that's 11 out of 17 cysteines used up right away. The sidechains on all these cysteines are locked.

The remaining cysteines 6, 20, 28, 137, 180, and 192. These aren't near one of the zincs, but I also get "sidechain locked" when I try to move their sidechains. So I think we're out of luck on making disulfide bridges in this one, all the cysteines are for something else.

Actually, most of the segments are locked in this one, but it can be a little hard to tell. The backbone is all unlocked, and there's no way in a recipe to tell whether a sidechain is locked. If you select EnzDes coloring, the backbone of the mutatable sections shows in in a lighter color, and locked sidechains are gray. The mutatable sidechains are unlocked. It looks like all the other sidechains are locked. The mutatable segments are all near the small molecule at segment 249.

The recipe Missing Ligand 1.0.1 -- brow42 can band cases like the zinc atoms when the ligand is missing from the puzzle. Unfortunately, it does only one spot, and this puzzle has three. If you run it, select "MCys4 (4-sided die)", then pick Zn as the metal atom. It makes a nice cage of bands around the zinc at segment 250. I'm not sure the recipe covers the exact case of 250 and 251 being stabilized by 7 cysteines. I'll see if I can find what that configuration is called.

Meanwhile, the small molecule at segment 249 is the focus of the puzzle. In that way, this one is similar to the aflatoxin puzzle, 1440.

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Developed by: UW Center for Game Science, UW Institute for Protein Design, Northeastern University, Vanderbilt University Meiler Lab, UC Davis
Supported by: DARPA, NSF, NIH, HHMI, Amazon, Microsoft, Adobe, RosettaCommons