1mik

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|PDB= 1mik |SIZE=350|CAPTION= <scene name='initialview01'>1mik</scene>, resolution 1.76&Aring;
|PDB= 1mik |SIZE=350|CAPTION= <scene name='initialview01'>1mik</scene>, resolution 1.76&Aring;
|SITE=
|SITE=
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|LIGAND=
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|LIGAND= <scene name='pdbligand=AA4:2-AMINO-5-HYDROXYPENTANOIC+ACID'>AA4</scene>, <scene name='pdbligand=BMT:4-METHYL-4-[(E)-2-BUTENYL]-4,N-METHYL-THREONINE'>BMT</scene>, <scene name='pdbligand=DAL:D-ALANINE'>DAL</scene>, <scene name='pdbligand=MLE:N-METHYLLEUCINE'>MLE</scene>, <scene name='pdbligand=MVA:N-METHYLVALINE'>MVA</scene>, <scene name='pdbligand=SAR:SARCOSINE'>SAR</scene>
|ACTIVITY=
|ACTIVITY=
|GENE= CYCLOPHILIN ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
|GENE= CYCLOPHILIN ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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|DOMAIN=
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|RELATEDENTRY=
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1mik FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mik OCA], [http://www.ebi.ac.uk/pdbsum/1mik PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1mik RCSB]</span>
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}}
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[[Category: complex (isomerase/immunosuppressant)]]
[[Category: complex (isomerase/immunosuppressant)]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:43:52 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:16:29 2008''

Revision as of 19:16, 30 March 2008


PDB ID 1mik

Drag the structure with the mouse to rotate
, resolution 1.76Å
Ligands: , , , , ,
Gene: CYCLOPHILIN (Homo sapiens)
Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



THE ROLE OF WATER MOLECULES IN THE STRUCTURE-BASED DESIGN OF (5-HYDROXYNORVALINE)-2-CYCLOSPORIN: SYNTHESIS, BIOLOGICAL ACTIVITY, AND CRYSTALLOGRAPHIC ANALYSIS WITH CYCLOPHILIN A


Overview

Analysis of the contact surface of the cyclophilin A (CypA)/cyclosporin A (CsA, 1) crystal structure delineates a unique cavity between both molecules in the vicinity of the Abu-2 side chain atoms of 1 (Abu pocket). Therefore, (5-hydroxynorvaline)-2-cyclosporin (2) was designed and prepared as a CsA derivative which could mediate additional interactions within the pocket. The X-ray crystal structure of the CypA/2 complex at 1.76 A resolution shows that 1 and 2 have identical backbone conformations and that the introduced hydroxypropyl chain makes indeed the expected supplemental interactions with CypA. However, 2 has 8-9-fold lower binding affinity than 1 for CypA. This results from a presumed unfavorable free energy change associated with the displacement of one of the tightly bound water molecules within the pocket and a change in prebinding equilibria. The role of the later was assessed by comparing the conformation distribution of 1 and 2 to that of norvaline-2-cyclosporin (3) and norvaline-2-(D-MeSer)-3-cyclosporin (4).

About this Structure

1MIK is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

The role of water molecules in the structure-based design of (5-hydroxynorvaline)-2-cyclosporin: synthesis, biological activity, and crystallographic analysis with cyclophilin A., Mikol V, Papageorgiou C, Borer X, J Med Chem. 1995 Aug 18;38(17):3361-7. PMID:7650689

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