5IUZ

STRUCTURE OF P450 2B4 F202W MUTANT (CYMAL-5)

Summary for 5IUZ

• Entry DOI: 10.2210/pdb5iuz/pdb
• Related: 1PO5 1SUO 2BDM 2Q6N 3G5N 3G93 3KW4 3ME6 3MVR 3R1A 3R1B 3TK3 3TMZ 3UAS 4H1N 4JLT 5EM4 5IUT
• Descriptor: Cytochrome P450 2B4, PROTOPORPHYRIN IX CONTAINING FE, 5-CYCLOHEXYL-1-PENTYL-BETA-D-MALTOSIDE, ... (4 entities in total)
• Functional Keywords: monooxygenase, membrane protein, oxidoreductase
• Biological source: Oryctolagus cuniculus (Rabbit)
• Cellular location: Endoplasmic reticulum membrane; Peripheral membrane protein: P00178
• Total number of polymer chains: 2
• Total formula weight: 112180.08

Authors

Jang, H.-H.,Halpert, J.R.,Shah, M.B. (deposition date: 2016-03-18, release date: 2016-06-08, Last modification date: 2023-09-27)

Primary citation

Shah, M.B.,Jang, H.H.,Wilderman, P.R.,Lee, D.,Li, S.,Zhang, Q.,Stout, C.D.,Halpert, J.R.
Effect of detergent binding on cytochrome P450 2B4 structure as analyzed by X-ray crystallography and deuterium-exchange mass spectrometry.
Biophys.Chem., 216:1-8, 2016

PubMed Abstract: Multiple crystal structures of CYP2B4 have demonstrated the binding of the detergent 5-cyclohexyl-1-pentyl-β-D-maltoside (CYMAL-5) in a peripheral pocket located adjacent to the active site. To explore the consequences of detergent binding, X-ray crystal structures of the peripheral pocket mutant CYP2B4 F202W were solved in the presence of hexaethylene glycol monooctyl ether (C8E6) and CYMAL-5. The structure in the presence of CYMAL-5 illustrated a closed conformation indistinguishable from the previously solved wild-type. In contrast, the F202W structure in the presence of C8E6 revealed a detergent molecule that coordinated the heme-iron and extended to the protein surface through the substrate access channel 2f. Despite the overall structural similarity of these detergent complexes, remarkable differences were observed in the A, A', and H helices, the F-G cassette, the C-D and β4 loop region. Hydrogen-deuterium exchange mass spectrometry (DXMS) was employed to probe these differences and to test the effect of detergents in solution. The presence of either detergent increased the H/D exchange rate across the plastic regions, and the results obtained by DXMS in solution were consistent in general with the relevant structural snapshots. The study provides insight into effect of detergent binding and the interpretation of associated conformational dynamics of CYP2B4.

PubMed: 27280734
DOI: 10.1016/j.bpc.2016.05.007

Experimental method

X-RAY DIFFRACTION (2.73 Å)