Structure and function of CYP108D1 from Novosphingobium aromaticivorans DSM12444: An aromatic hydrocarbon-binding P450 enzyme
CYP108D1 from Novosphingobium aromaticivorans DSM12444 binds a range of aromatic hydrocarbons such as phenanthrene, biphenyl and phenylcyclohexane. Its structure, which is reported here at 2.2 Å resolution, is closely related to that of CYP108A1 (P450terp), an -terpineol-oxidizing enzyme. The compos...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2012
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| _version_ | 1826274439969374208 |
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| author | Bell, S Yang, W Yorke, J Zhou, W Wang, H Harmer, J Copley, R Zhang, A Zhou, R Bartlam, M Rao, Z Wong, L |
| author_facet | Bell, S Yang, W Yorke, J Zhou, W Wang, H Harmer, J Copley, R Zhang, A Zhou, R Bartlam, M Rao, Z Wong, L |
| author_sort | Bell, S |
| collection | OXFORD |
| description | CYP108D1 from Novosphingobium aromaticivorans DSM12444 binds a range of aromatic hydrocarbons such as phenanthrene, biphenyl and phenylcyclohexane. Its structure, which is reported here at 2.2 Å resolution, is closely related to that of CYP108A1 (P450terp), an -terpineol-oxidizing enzyme. The compositions and structures of the active sites of these two enzymes are very similar; the most significant changes are the replacement of Glu77 and Thr103 in CYP108A1 by Thr79 and Val105 in CYP108D1. Other residue differences lead to a larger and more hydrophobic access channel in CYP108D1. These structural features are likely to account for the weaker - terpineol binding by CYP108D1 and, when combined with the presence of three hydrophobic phenylalanine residues in the active site, promote the binding of aromatic hydrocarbons. The haem-proximal surface of CYP108D1 shows a different charge distribution and topology to those of CYP101D1, CYP101A1 and CYP108A1, including a pronounced kink in the proximal loop of CYP108D1, which may result in poor complementarity with the [2Fe-2S] ferredoxins Arx, putida-redoxin and terpredoxin that are the respective redox partners of these three P450 enzymes. The unexpectedly low reduction potential of phenylcyclohexane-bound CYP108D1 (-401 mV) may also contribute to the low activity observed with these ferredoxins. CYP108D1 appears to function as an aromatic hydrocarbon hydroxylase that requires a different electron-transfer cofactor protein. © 2012 International Union of Crystallography Printed in Singapore - all rights reserved. |
| first_indexed | 2024-03-06T22:43:27Z |
| format | Journal article |
| id | oxford-uuid:5c5bb2c2-87d7-4852-a36c-9edcd61f5a50 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:43:27Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:5c5bb2c2-87d7-4852-a36c-9edcd61f5a502022-03-26T17:27:49ZStructure and function of CYP108D1 from Novosphingobium aromaticivorans DSM12444: An aromatic hydrocarbon-binding P450 enzymeJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:5c5bb2c2-87d7-4852-a36c-9edcd61f5a50EnglishSymplectic Elements at Oxford2012Bell, SYang, WYorke, JZhou, WWang, HHarmer, JCopley, RZhang, AZhou, RBartlam, MRao, ZWong, LCYP108D1 from Novosphingobium aromaticivorans DSM12444 binds a range of aromatic hydrocarbons such as phenanthrene, biphenyl and phenylcyclohexane. Its structure, which is reported here at 2.2 Å resolution, is closely related to that of CYP108A1 (P450terp), an -terpineol-oxidizing enzyme. The compositions and structures of the active sites of these two enzymes are very similar; the most significant changes are the replacement of Glu77 and Thr103 in CYP108A1 by Thr79 and Val105 in CYP108D1. Other residue differences lead to a larger and more hydrophobic access channel in CYP108D1. These structural features are likely to account for the weaker - terpineol binding by CYP108D1 and, when combined with the presence of three hydrophobic phenylalanine residues in the active site, promote the binding of aromatic hydrocarbons. The haem-proximal surface of CYP108D1 shows a different charge distribution and topology to those of CYP101D1, CYP101A1 and CYP108A1, including a pronounced kink in the proximal loop of CYP108D1, which may result in poor complementarity with the [2Fe-2S] ferredoxins Arx, putida-redoxin and terpredoxin that are the respective redox partners of these three P450 enzymes. The unexpectedly low reduction potential of phenylcyclohexane-bound CYP108D1 (-401 mV) may also contribute to the low activity observed with these ferredoxins. CYP108D1 appears to function as an aromatic hydrocarbon hydroxylase that requires a different electron-transfer cofactor protein. © 2012 International Union of Crystallography Printed in Singapore - all rights reserved. |
| spellingShingle | Bell, S Yang, W Yorke, J Zhou, W Wang, H Harmer, J Copley, R Zhang, A Zhou, R Bartlam, M Rao, Z Wong, L Structure and function of CYP108D1 from Novosphingobium aromaticivorans DSM12444: An aromatic hydrocarbon-binding P450 enzyme |
| title | Structure and function of CYP108D1 from Novosphingobium aromaticivorans DSM12444: An aromatic hydrocarbon-binding P450 enzyme |
| title_full | Structure and function of CYP108D1 from Novosphingobium aromaticivorans DSM12444: An aromatic hydrocarbon-binding P450 enzyme |
| title_fullStr | Structure and function of CYP108D1 from Novosphingobium aromaticivorans DSM12444: An aromatic hydrocarbon-binding P450 enzyme |
| title_full_unstemmed | Structure and function of CYP108D1 from Novosphingobium aromaticivorans DSM12444: An aromatic hydrocarbon-binding P450 enzyme |
| title_short | Structure and function of CYP108D1 from Novosphingobium aromaticivorans DSM12444: An aromatic hydrocarbon-binding P450 enzyme |
| title_sort | structure and function of cyp108d1 from novosphingobium aromaticivorans dsm12444 an aromatic hydrocarbon binding p450 enzyme |
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