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| | {{STRUCTURE_1mcd| PDB=1mcd | SCENE= }} | | {{STRUCTURE_1mcd| PDB=1mcd | SCENE= }} |
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| - | '''PRINCIPLES AND PITFALLS IN DESIGNING SITE DIRECTED PEPTIDE LIGANDS'''
| + | ===PRINCIPLES AND PITFALLS IN DESIGNING SITE DIRECTED PEPTIDE LIGANDS=== |
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| - | ==Overview==
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| - | An immunoglobulin light chain dimer with a large generic binding cavity was used as a host molecule for designing a series of peptide guest ligands. In a screening procedure peptides coupled to solid supports were systematically tested for binding activity by enzyme linked immunosorbent assays (ELISA). Key members of the binding series were synthesized in milligram quantities and diffused into crystals of the host molecule for X-ray analyses. These peptides were incrementally increased in size and affinity until they nearly filled the cavity. Progressive changes in binding patterns were mapped by comparisons of crystallographically refined structures of 14 peptide-protein complexes at 2.7 A resolution. These comparisons led to guidelines for ligand design and also suggested ways to modify previously established binding patterns. By manipulating equilibria involving histidine, for example, it was possible to abolish one important intramolecular interaction of the bound ligand and substitute another. These events triggered a change in conformation of the ligand from a compact to an extended form and a comprehensive change in the mode of binding to the protein. In dipeptides of histidine and proline, protonation of both imidazolium nitrogen atoms was used to program an end-to-end reversal of the direction in which the ligand was inserted into the binding cavity. Peptides cocrystallized with proteins produced complexes somewhat different in structure from those in which ligands were diffused into preexisting crystals. In such a large and malleable cavity, space utilization was thus different when a ligand was introduced before the imposition of crystal packing restraints.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_8346191}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 8346191 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_8346191}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Harris, D L.]] | | [[Category: Harris, D L.]] |
| | [[Category: Immunoglobulin]] | | [[Category: Immunoglobulin]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 00:53:08 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 2 23:40:35 2008'' |
Revision as of 20:40, 2 July 2008
Template:STRUCTURE 1mcd
PRINCIPLES AND PITFALLS IN DESIGNING SITE DIRECTED PEPTIDE LIGANDS
Template:ABSTRACT PUBMED 8346191
About this Structure
1MCD is a Single protein structure. Full crystallographic information is available from OCA.
Reference
Principles and pitfalls in designing site-directed peptide ligands., Edmundson AB, Harris DL, Fan ZC, Guddat LW, Schley BT, Hanson BL, Tribbick G, Geysen HM, Proteins. 1993 Jul;16(3):246-67. PMID:8346191
Page seeded by OCA on Wed Jul 2 23:40:35 2008
