The crystal structure of isopenicillin N synthase with δ-((L)-α-aminoadipoyl)-(L)-cysteinyl-(D)-methionine reveals thioether coordination to iron.
Isopenicillin N synthase (IPNS) catalyses cyclization of δ-(l-α-aminoadipoyl)-l-cysteinyl-d-valine (ACV) to isopenicillin N (IPN), the central step in penicillin biosynthesis. Previous studies have shown that IPNS turns over a wide range of substrate analogues in which the valine residue of its natu...
| Những tác giả chính: | , , , , |
|---|---|
| Định dạng: | Journal article |
| Ngôn ngữ: | English |
| Được phát hành: |
2011
|
| _version_ | 1826263804297609216 |
|---|---|
| author | Clifton, I Ge, W Adlington, R Baldwin, J Rutledge, P |
| author_facet | Clifton, I Ge, W Adlington, R Baldwin, J Rutledge, P |
| author_sort | Clifton, I |
| collection | OXFORD |
| description | Isopenicillin N synthase (IPNS) catalyses cyclization of δ-(l-α-aminoadipoyl)-l-cysteinyl-d-valine (ACV) to isopenicillin N (IPN), the central step in penicillin biosynthesis. Previous studies have shown that IPNS turns over a wide range of substrate analogues in which the valine residue of its natural substrate is replaced with other amino acids. IPNS accepts and oxidizes numerous substrates that bear hydrocarbon sidechains in this position, however the enzyme is less tolerant of analogues presenting polar functionality in place of the valinyl isopropyl group. We report a new ACV analogue δ-(l-α-aminoadipoyl)-l-cysteinyl-d-methionine (ACM), which incorporates a thioether in place of the valinyl sidechain. ACM has been synthesized using solution phase methods and crystallized with IPNS. A crystal structure has been elucidated for the IPNS:Fe(II):ACM complex at 1.40Å resolution. This structure reveals that ACM binds in the IPNS active site such that the sulfur atom of the methionine thioether binds to iron in the oxygen binding site at a distance of 2.57Å. The sulfur of the cysteinyl thiolate sits 2.36Å from the metal. |
| first_indexed | 2024-03-06T19:57:40Z |
| format | Journal article |
| id | oxford-uuid:2633c46b-9a4b-4541-b067-058aee29b118 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:57:40Z |
| publishDate | 2011 |
| record_format | dspace |
| spelling | oxford-uuid:2633c46b-9a4b-4541-b067-058aee29b1182022-03-26T11:59:34ZThe crystal structure of isopenicillin N synthase with δ-((L)-α-aminoadipoyl)-(L)-cysteinyl-(D)-methionine reveals thioether coordination to iron.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:2633c46b-9a4b-4541-b067-058aee29b118EnglishSymplectic Elements at Oxford2011Clifton, IGe, WAdlington, RBaldwin, JRutledge, PIsopenicillin N synthase (IPNS) catalyses cyclization of δ-(l-α-aminoadipoyl)-l-cysteinyl-d-valine (ACV) to isopenicillin N (IPN), the central step in penicillin biosynthesis. Previous studies have shown that IPNS turns over a wide range of substrate analogues in which the valine residue of its natural substrate is replaced with other amino acids. IPNS accepts and oxidizes numerous substrates that bear hydrocarbon sidechains in this position, however the enzyme is less tolerant of analogues presenting polar functionality in place of the valinyl isopropyl group. We report a new ACV analogue δ-(l-α-aminoadipoyl)-l-cysteinyl-d-methionine (ACM), which incorporates a thioether in place of the valinyl sidechain. ACM has been synthesized using solution phase methods and crystallized with IPNS. A crystal structure has been elucidated for the IPNS:Fe(II):ACM complex at 1.40Å resolution. This structure reveals that ACM binds in the IPNS active site such that the sulfur atom of the methionine thioether binds to iron in the oxygen binding site at a distance of 2.57Å. The sulfur of the cysteinyl thiolate sits 2.36Å from the metal. |
| spellingShingle | Clifton, I Ge, W Adlington, R Baldwin, J Rutledge, P The crystal structure of isopenicillin N synthase with δ-((L)-α-aminoadipoyl)-(L)-cysteinyl-(D)-methionine reveals thioether coordination to iron. |
| title | The crystal structure of isopenicillin N synthase with δ-((L)-α-aminoadipoyl)-(L)-cysteinyl-(D)-methionine reveals thioether coordination to iron. |
| title_full | The crystal structure of isopenicillin N synthase with δ-((L)-α-aminoadipoyl)-(L)-cysteinyl-(D)-methionine reveals thioether coordination to iron. |
| title_fullStr | The crystal structure of isopenicillin N synthase with δ-((L)-α-aminoadipoyl)-(L)-cysteinyl-(D)-methionine reveals thioether coordination to iron. |
| title_full_unstemmed | The crystal structure of isopenicillin N synthase with δ-((L)-α-aminoadipoyl)-(L)-cysteinyl-(D)-methionine reveals thioether coordination to iron. |
| title_short | The crystal structure of isopenicillin N synthase with δ-((L)-α-aminoadipoyl)-(L)-cysteinyl-(D)-methionine reveals thioether coordination to iron. |
| title_sort | crystal structure of isopenicillin n synthase with δ l α aminoadipoyl l cysteinyl d methionine reveals thioether coordination to iron |
| work_keys_str_mv | AT cliftoni thecrystalstructureofisopenicillinnsynthasewithdlaaminoadipoyllcysteinyldmethioninerevealsthioethercoordinationtoiron AT gew thecrystalstructureofisopenicillinnsynthasewithdlaaminoadipoyllcysteinyldmethioninerevealsthioethercoordinationtoiron AT adlingtonr thecrystalstructureofisopenicillinnsynthasewithdlaaminoadipoyllcysteinyldmethioninerevealsthioethercoordinationtoiron AT baldwinj thecrystalstructureofisopenicillinnsynthasewithdlaaminoadipoyllcysteinyldmethioninerevealsthioethercoordinationtoiron AT rutledgep thecrystalstructureofisopenicillinnsynthasewithdlaaminoadipoyllcysteinyldmethioninerevealsthioethercoordinationtoiron AT cliftoni crystalstructureofisopenicillinnsynthasewithdlaaminoadipoyllcysteinyldmethioninerevealsthioethercoordinationtoiron AT gew crystalstructureofisopenicillinnsynthasewithdlaaminoadipoyllcysteinyldmethioninerevealsthioethercoordinationtoiron AT adlingtonr crystalstructureofisopenicillinnsynthasewithdlaaminoadipoyllcysteinyldmethioninerevealsthioethercoordinationtoiron AT baldwinj crystalstructureofisopenicillinnsynthasewithdlaaminoadipoyllcysteinyldmethioninerevealsthioethercoordinationtoiron AT rutledgep crystalstructureofisopenicillinnsynthasewithdlaaminoadipoyllcysteinyldmethioninerevealsthioethercoordinationtoiron |