Homework9

HOMEWORK 9

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Answers are also available at that URL.)

You wish to build a model of a signaling protein that you have discovered has an SH2 domain so that you can predict suitable mutations to alter its enzymatic effect. To begin, you need to determine whether the structure of this protein has already been determined. Identify the sequence's accession number and then use Entrez to determine whether there is a structure for this molecule. If there isn't, you'll need to build a model.

In order to build the model, you will have to thread the sequence to identify appropriate templates. Unfortunately, the sequence is very long and would take any extremely long time to thread. Therefore, you decide to model only the SH2 domain. Use a domain searching tool to locate the position of the phosphatase within your protein (for example, submit the sequence to http://pfam.wustl.edu). Once you have located the position of the phosphatase, trim the sequence accordingly so that it only encompasses that region. (~100aa). Submit this portion of the sequence to a web-based threading utility like http://123d.ncifcrf.gov/123D+.html. The results will be e-mailed back to you a couple of hours later. When you receive the results, pick the top 2-3 templates to use for model building.
Build your model using SWISS-MODEL. You will need to submit your phosphatase domain sequence and the names of your templates.

Open the PDB file that was sent to you as an attachment using one of the molecular visualization applications discussed in lecture. Lastly, use DALI to find related structures to your model.

SEQUENCE TO MODEL:

>sh2Protein
MSQWYELQQLDSKFLEQVHQLYDDSFPMEIRQYLAQWLEKQDWEHAANDVSFATIRFHDLLSQLDDQYSR
FSLENNFLLQHNIRKSKRNLQDNFQEDPIQMSMIIYSCLKEERKILENAQRFNQAQSGNIQSTVMLDKQK
ELDSKVRNVKDKVMCIEHEIKSLEDLQDEYDFKCKTLQNREHETNGVAKSDQKQEQLLLKKMYLMLDNKR
KEVVHKIIELLNVTELTQNALINDELVEWKRRQQSACIGGPPNACLDQLQNWFTIVAESLQQVRQQLKKL
EELEQKYTYEHDPITKNKQVLWDRTFSLFQQLIQSSFVVERQPCMPTHPQRPLVLKTGVQFTVKLRLLVK
LQELNYNLKVKVLFDKDVNERNTVKGFRKFNILGTHTKVMNMEESTNGSLAAEFRHLQLKEQKNAGTRTN
EGPLIVTEELHSLSFETQLCQPGLVIDLETTSLPVVVISNVSQLPSGWASILWYNMLVAEPRNLSFFLTP
PCARWAQLSEVLSWQFSSVTKRGLNVDQLNMLGEKLLGPNASPDGLIPWTRFCKENINDKNFPFWLWIES
ILELIKKHLLPLWNDGCIMGFISKERERALLKDQQPGTFLLRFSESSREGAITFTWVERSQNGGEPDFHA
VEPYTKKELSAVTFPDIIRNYKVMAAENIPENPLKYLYPNIDKDHAFGKYYSRPKEAPEPMELDGPKGTG
YIKTELISVSEVHPSRLQTTDNLLPMSPEEFDEVSRIVGSVEFDSMMNTV

HOMEWORK 9

(For interactive page, go to /education/bioinfo Answers are also available at that URL.)

(For interactive page, go to /education/bioinfo
Answers are also available at that URL.)