2as2
From Proteopedia
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|PDB= 2as2 |SIZE=350|CAPTION= <scene name='initialview01'>2as2</scene>, resolution 1.45Å | |PDB= 2as2 |SIZE=350|CAPTION= <scene name='initialview01'>2as2</scene>, resolution 1.45Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=2IM:PIPERIDIN-2-IMINE'>2IM</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Cytochrome-c_peroxidase Cytochrome-c peroxidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.11.1.5 1.11.1.5] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Cytochrome-c_peroxidase Cytochrome-c peroxidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.11.1.5 1.11.1.5] </span> |
|GENE= CCP1, CCP, CPO ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 Saccharomyces cerevisiae]) | |GENE= CCP1, CCP, CPO ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 Saccharomyces cerevisiae]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1aa4|1AA4]], [[2anz|2ANZ]], [[2aqd|2AQD]], [[2as1|2AS1]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2as2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2as2 OCA], [http://www.ebi.ac.uk/pdbsum/2as2 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2as2 RCSB]</span> | ||
}} | }} | ||
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[[Category: Shoichet, B K.]] | [[Category: Shoichet, B K.]] | ||
[[Category: Vetter, S W.]] | [[Category: Vetter, S W.]] | ||
| - | [[Category: 2IM]] | ||
| - | [[Category: HEM]] | ||
[[Category: model binding site]] | [[Category: model binding site]] | ||
[[Category: oxidoreductase]] | [[Category: oxidoreductase]] | ||
[[Category: peroxidase]] | [[Category: peroxidase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:56:33 2008'' |
Revision as of 22:56, 30 March 2008
| |||||||
| , resolution 1.45Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Gene: | CCP1, CCP, CPO (Saccharomyces cerevisiae) | ||||||
| Activity: | Cytochrome-c peroxidase, with EC number 1.11.1.5 | ||||||
| Related: | 1AA4, 2ANZ, 2AQD, 2AS1
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
cytochrome c peroxidase in complex with 2-iminopiperidine
Overview
A model binding site was used to investigate charge-charge interactions in molecular docking. This simple site, a small (180A(3)) engineered cavity in cyctochrome c peroxidase (CCP), is negatively charged and completely buried from solvent, allowing us to explore the balance between electrostatic energy and ligand desolvation energy in a system where many of the common approximations in docking do not apply. A database with about 5300 molecules was docked into this cavity. Retrospective testing with known ligands and decoys showed that overall the balance between electrostatic interaction and desolvation energy was captured. More interesting were prospective docking scre"ens that looked for novel ligands, especially those that might reveal problems with the docking and energy methods. Based on screens of the 5300 compound database, both high-scoring and low-scoring molecules were acquired and tested for binding. Out of 16 new, high-scoring compounds tested, 15 were observed to bind. All of these were small heterocyclic cations. Binding constants were measured for a few of these, they ranged between 20microM and 60microM. Crystal structures were determined for ten of these ligands in complex with the protein. The observed ligand geometry corresponded closely to that predicted by docking. Several low-scoring alkyl amino cations were also tested and found to bind. The low docking score of these molecules owed to the relatively high charge density of the charged amino group and the corresponding high desolvation penalty. When the complex structures of those ligands were determined, a bound water molecule was observed interacting with the amino group and a backbone carbonyl group of the cavity. This water molecule mitigates the desolvation penalty and improves the interaction energy relative to that of the "naked" site used in the docking screen. Finally, six low-scoring neutral molecules were also tested, with a view to looking for false negative predictions. Whereas most of these did not bind, two did (phenol and 3-fluorocatechol). Crystal structures for these two ligands in complex with the cavity site suggest reasons for their binding. That these neutral molecules do, in fact bind, contradicts previous results in this site and, along with the alkyl amines, provides instructive false negatives that help identify weaknesses in our scoring functions. Several improvements of these are considered.
About this Structure
2AS2 is a Single protein structure of sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA.
Reference
Probing molecular docking in a charged model binding site., Brenk R, Vetter SW, Boyce SE, Goodin DB, Shoichet BK, J Mol Biol. 2006 Apr 14;357(5):1449-70. Epub 2006 Feb 2. PMID:16490206
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