2c7x
From Proteopedia
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|PDB= 2c7x |SIZE=350|CAPTION= <scene name='initialview01'>2c7x</scene>, resolution 1.75Å | |PDB= 2c7x |SIZE=350|CAPTION= <scene name='initialview01'>2c7x</scene>, resolution 1.75Å | ||
|SITE= <scene name='pdbsite=AC1:Nrb+Binding+Site+For+Chain+A'>AC1</scene> | |SITE= <scene name='pdbsite=AC1:Nrb+Binding+Site+For+Chain+A'>AC1</scene> | ||
| - | |LIGAND= <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene> | + | |LIGAND= <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=NRB:NARBOMYCIN'>NRB</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2c7x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2c7x OCA], [http://www.ebi.ac.uk/pdbsum/2c7x PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2c7x RCSB]</span> | ||
}} | }} | ||
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[[Category: Waterman, M R.]] | [[Category: Waterman, M R.]] | ||
[[Category: Yermalitskaya, L V.]] | [[Category: Yermalitskaya, L V.]] | ||
| - | [[Category: HEM]] | ||
| - | [[Category: NRB]] | ||
[[Category: antibiotic biosynthesis]] | [[Category: antibiotic biosynthesis]] | ||
[[Category: cytochrome p450]] | [[Category: cytochrome p450]] | ||
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[[Category: pikc]] | [[Category: pikc]] | ||
| - | ''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 02:17:38 2008'' |
Revision as of 23:17, 30 March 2008
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| , resolution 1.75Å | |||||||
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| Sites: | |||||||
| Ligands: | , | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTAL STRUCTURE OF NARBOMYCIN-BOUND CYTOCHROME P450 PIKC (CYP107L1)
Overview
The pikromycin (Pik)/methymycin biosynthetic pathway of Streptomyces venezuelae represents a valuable system for dissecting the fundamental mechanisms of modular polyketide biosynthesis, aminodeoxysugar assembly, glycosyltransfer, and hydroxylation leading to the production of a series of macrolide antibiotics, including the natural ketolides narbomycin and pikromycin. In this study, we describe four x-ray crystal structures and allied functional studies for PikC, the remarkable P450 monooxygenase responsible for production of a number of related macrolide products from the Pik pathway. The results provide important new insights into the structural basis for the C10/C12 and C12/C14 hydroxylation patterns for the 12-(YC-17) and 14-membered ring (narbomycin) macrolides, respectively. This includes two different ligand-free structures in an asymmetric unit (resolution 2.1 A) and two co-crystal structures with bound endogenous substrates YC-17 (resolution 2.35 A)or narbomycin (resolution 1.7 A). A central feature of the enzyme-substrate interaction involves anchoring of the desosamine residue in two alternative binding pockets based on a series of distinct amino acid residues that form a salt bridge and a hydrogen-bonding network with the deoxysugar C3' dimethylamino group. Functional significance of the salt bridge was corroborated by site-directed mutagenesis that revealed a key role for Glu-94 in YC-17 binding and Glu-85 for narbomycin binding. Taken together, the x-ray structure analysis, site-directed mutagenesis, and corresponding product distribution studies reveal that PikC substrate tolerance and product diversity result from a combination of alternative anchoring modes rather than an induced fit mechanism.
About this Structure
2C7X is a Single protein structure of sequence from Streptomyces venezuelae. Full crystallographic information is available from OCA.
Reference
The structural basis for substrate anchoring, active site selectivity, and product formation by P450 PikC from Streptomyces venezuelae., Sherman DH, Li S, Yermalitskaya LV, Kim Y, Smith JA, Waterman MR, Podust LM, J Biol Chem. 2006 Sep 8;281(36):26289-97. Epub 2006 Jul 6. PMID:16825192
Page seeded by OCA on Mon Mar 31 02:17:38 2008
Categories: Single protein | Streptomyces venezuelae | Kim, Y. | Li, S. | Podust, L M. | Sherman, D H. | Smith, J A. | Waterman, M R. | Yermalitskaya, L V. | Antibiotic biosynthesis | Cytochrome p450 | Heme | Iron | Macrolide monooxygenase | Metal-binding | Monooxygenase | Narbomycin | Oxidoreductase | Pikc
