Biochemistry on the Internet

10. Protein Modeling on the Internet A group of patients suffering from Crohn's disease (an inflammatory bowel disease) underwent biopsies of their intestinal mucosa in an attempt to identify the causative agent. A protein was identified that was expressed at higher levels in patients with Crohn's disease than in patients with an unrelated inflammatory bowel disease or in unaffected controls. The protein was isolated and the following partial amino acid sequence was obtained (reads left to right):

EAELCPDRCI HSFQNLGIQC VKKRDLEQAI

SQRIQTNNNP FQVPIEEQRG DYDLNAVRLC

FQVTVRDPSG RPLRLPPVLP HPIFDNRAPN

TAELKICRVN RNSGSCLGGD EIFLLCDKVQ

KEDIEVYFTG PGWEARGSFS QADVHRQVAI

VFRTPPYADP SLQAPVRVSM QLRRPSDREL

SEPMEFQYLP DTDDRHRIEE KRKRTYETFK

SIMKKSPFSG PTDPRPPPRR IAVPSRSSAS VPKPAPQPYP

(a) You can identify this protein using a protein database on the Internet. Some good places to start include Protein Information Resource (PIR; pir.georgetown.edu/ pirwww), Structural Classification of Proteins (SCOP; http:// scop.berkeley.edu), and Prosite (http://us.expasy.org/prosite).

At your selected database site, follow links to locate the sequence comparison engine. Enter about 30 residues from the sequence of the protein in the appropriate search field and submit it for analysis. What does this analysis tell you about the identity of the protein?

(b) Try using different portions of the protein amino acid sequence. Do you always get the same result?

(c) A variety of websites provide information about the three-dimensional structure of proteins. Find information about the protein's secondary, tertiary, and quaternary structure using database sites such as the Protein Data Bank (PDB; www.rcsb.org/pdb) or SCOP.

(d) In the course of your Web searches try to find information about the cellular function of the protein.

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