1sm3: Difference between revisions

Revision as of 16:02, 21 February 2008

CRYSTAL STRUCTURE OF THE TUMOR SPECIFIC ANTIBODY SM3 COMPLEX WITH ITS PEPTIDE EPITOPE

OverviewOverview

The anti-breast tumour antibody SM3 has a high selectivity in reacting specifically with carcinoma-associated mucin. SM3 recognises the core repeating motif (Pro-Asp-Thr-Arg-Pro) of aberrantly glycosylated epithelial mucin MUC1, and has potential as a therapeutic and diagnostic tool. Here we report the crystal structure of the Fab fragment of SM3 in complex with a 13-residue MUC1 peptide antigen (Thr1P-Ser2P-Ala3P-Pro4P-Asp5P-Thr6P -Arg7P-Pro8P-Ala9P-Pro10P-Gly11P- Ser12P-Thr13P). The SM3-MUC1 peptide structure was solved by molecular replacement, and the current model is refined at 1.95 A resolution with an R-factor of 21.3% and R-free 28.3%. The MUC1 peptide is bound both by non-polar interactions and hydrogen bonds in an elongated groove in the antibody-combining site through interactions with Complimentarity Determining Regions (CDRs), three of the light chain (L1, L2, L3) and two of the heavy chain (H1 and H3). The conformation of the peptide is mainly extended with no discernable standard secondary structure. There is a single non-proline cis-peptide bond in H3 (Val95H-Gly96H-Gln97H-Phe98H-Ala101H-Ty r102H) between Gly96H and Gln97H, which appears to play a role in SM3-peptide antigen interactions, and represents the first such example within an antibody hypervariable loop. The SM3-MUC1 peptide structure has implications for rational therapeutic and diagnostic antibody engineering.

About this StructureAbout this Structure

1SM3 is a Protein complex structure of sequences from Mus musculus with and as ligands. Full crystallographic information is available from OCA.

ReferenceReference

Crystal structure at 1.95 A resolution of the breast tumour-specific antibody SM3 complexed with its peptide epitope reveals novel hypervariable loop recognition., Dokurno P, Bates PA, Band HA, Stewart LM, Lally JM, Burchell JM, Taylor-Papadimitriou J, Snary D, Sternberg MJ, Freemont PS, J Mol Biol. 1998 Dec 4;284(3):713-28. PMID:9826510

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OCA

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-[[Image:1sm3.gif|left|200px]]<br />
+[[Image:1sm3.gif|left|200px]]<br /><applet load="1sm3" size="350" color="white" frame="true" align="right" spinBox="true"
-<applet load="1sm3" size="450" color="white" frame="true" align="right" spinBox="true"
 caption="1sm3, resolution 1.95&Aring;" />
 '''CRYSTAL STRUCTURE OF THE TUMOR SPECIFIC ANTIBODY SM3 COMPLEX WITH ITS PEPTIDE EPITOPE'''<br />
 ==Overview==
-The anti-breast tumour antibody SM3 has a high selectivity in reacting, specifically with carcinoma-associated mucin. SM3 recognises the core, repeating motif (Pro-Asp-Thr-Arg-Pro) of aberrantly glycosylated, epithelial mucin MUC1, and has potential as a therapeutic and diagnostic, tool. Here we report the crystal structure of the Fab fragment of SM3 in, complex with a 13-residue MUC1 peptide antigen, (Thr1P-Ser2P-Ala3P-Pro4P-Asp5P-Thr6P -Arg7P-Pro8P-Ala9P-Pro10P-Gly11P-, Ser12P-Thr13P). The SM3-MUC1 peptide structure was solved by molecular, replacement, and the current model is refined at 1.95 A resolution with an, R-factor of 21.3% and R-free 28.3%. The MUC1 peptide is bound both by, non-polar interactions and hydrogen bonds in an elongated groove in the, antibody-combining site through interactions with Complimentarity, Determining Regions (CDRs), three of the light chain (L1, L2, L3) and two, of the heavy chain (H1 and H3). The conformation of the peptide is mainly, extended with no discernable standard secondary structure. There is a, single non-proline cis-peptide bond in H3, (Val95H-Gly96H-Gln97H-Phe98H-Ala101H-Ty r102H) between Gly96H and Gln97H, which appears to play a role in SM3-peptide antigen interactions, and, represents the first such example within an antibody hypervariable loop., The SM3-MUC1 peptide structure has implications for rational therapeutic, and diagnostic antibody engineering.
+The anti-breast tumour antibody SM3 has a high selectivity in reacting specifically with carcinoma-associated mucin. SM3 recognises the core repeating motif (Pro-Asp-Thr-Arg-Pro) of aberrantly glycosylated epithelial mucin MUC1, and has potential as a therapeutic and diagnostic tool. Here we report the crystal structure of the Fab fragment of SM3 in complex with a 13-residue MUC1 peptide antigen (Thr1P-Ser2P-Ala3P-Pro4P-Asp5P-Thr6P -Arg7P-Pro8P-Ala9P-Pro10P-Gly11P- Ser12P-Thr13P). The SM3-MUC1 peptide structure was solved by molecular replacement, and the current model is refined at 1.95 A resolution with an R-factor of 21.3% and R-free 28.3%. The MUC1 peptide is bound both by non-polar interactions and hydrogen bonds in an elongated groove in the antibody-combining site through interactions with Complimentarity Determining Regions (CDRs), three of the light chain (L1, L2, L3) and two of the heavy chain (H1 and H3). The conformation of the peptide is mainly extended with no discernable standard secondary structure. There is a single non-proline cis-peptide bond in H3 (Val95H-Gly96H-Gln97H-Phe98H-Ala101H-Ty r102H) between Gly96H and Gln97H, which appears to play a role in SM3-peptide antigen interactions, and represents the first such example within an antibody hypervariable loop. The SM3-MUC1 peptide structure has implications for rational therapeutic and diagnostic antibody engineering.
 ==About this Structure==
-SM3 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with CD and CL as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1SM3 OCA].
+SM3 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=CD:'>CD</scene> and <scene name='pdbligand=CL:'>CL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SM3 OCA].
 ==Reference==
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 [[Category: Mus musculus]]
 [[Category: Protein complex]]
-[[Category: Band, H.A.]]
+[[Category: Band, H A.]]
-[[Category: Bates, P.A.]]
+[[Category: Bates, P A.]]
-[[Category: Burchell, J.M.]]
+[[Category: Burchell, J M.]]
 [[Category: Dokurno, P.]]
-[[Category: Freemont, P.S.]]
+[[Category: Freemont, P S.]]
-[[Category: Lally, J.M.]]
+[[Category: Lally, J M.]]
 [[Category: Snary, D.]]
-[[Category: Sternberg, M.J.E.]]
+[[Category: Sternberg, M J.E.]]
-[[Category: Stewart, L.M.D.]]
+[[Category: Stewart, L M.D.]]
 [[Category: Taylor-Papadimitriou, J.]]
 [[Category: CD]]
@@ Line 31: / Line 30: @@
 [[Category: peptide antigen]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 19:15:26 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:02:56 2008''