1LWL

Crystal Structure of Cytochrome P450-cam with a Fluorescent Probe D-8-Ad (Adamantane-1-carboxylic acid-5-dimethylamino-naphthalene-1-sulfonylamino-octyl-amide)

Summary for 1LWL

• Entry DOI: 10.2210/pdb1lwl/pdb
• Related: 1K2O 1QMQ
• Descriptor: Cytochrome P450-cam, PROTOPORPHYRIN IX CONTAINING FE, ADAMANTANE-1-CARBOXYLIC ACID-5-DIMETHYLAMINO-NAPHTHALENE-1-SULFONYLAMINO-OCTYL-AMIDE, ... (4 entities in total)
• Functional Keywords: monooxygenase, electron transfer, energy transfer, substrate-binding, dansyl, adamantane, adamantane-1-carboxylic acid [4-(5-dimethylamino-naphthalene-1-sulfonylamino)-octyl]-amide, channel, oxidoreductase
• Biological source: Pseudomonas putida
• Cellular location: Cytoplasm (By similarity): P00183
• Total number of polymer chains: 1
• Total formula weight: 48117.62

Authors

Dunn, A.R.,Hays, A.M.,Goodin, D.B.,Stout, C.D.,Chiu, R.,Winkler, J.R.,Gray, H.B. (deposition date: 2002-05-31, release date: 2002-12-18, Last modification date: 2024-02-14)

Primary citation

Dunn, A.R.,Hays, A.M.,Goodin, D.B.,Stout, C.D.,Chiu, R.,Winkler, J.R.,Gray, H.B.
Fluorescent probes for cytochrome P450 structural characterization and inhibitor screening
J.AM.CHEM.SOC., 124:10254-10255, 2002

PubMed Abstract: We have synthesized two luminescent probes (D-4-Ad and D-8-Ad) that target cytochrome P450cam. D-4-Ad luminescence is quenched by Förster energy transfer upon binding (Kd = 0.83 muM) but is restored when the probe is displaced from the active site by camphor. In contrast, D-8-Ad (Kd approximately 0.02 muM) is not displaced from the enzyme, even in the presence of a large excess of camphor. The 2.2 A resolution crystal structure of the D-8-Ad:P450cam complex reveals extensive hydrophobic contacts between the probe and the enzyme, which result from the conformational flexibility of the B', F, and G helices. Probes with properties similar to those of D-4-Ad potentially could be useful for screening P450 inhibitors.

PubMed: 12197708
DOI: 10.1021/ja0271678

Experimental method

X-RAY DIFFRACTION (2.2 Å)