4E0U
Crystal structure of CdpNPT in complex with thiolodiphosphate and (S)-benzodiazependione
Summary for 4E0U
| Entry DOI | 10.2210/pdb4e0u/pdb |
| Related | 4E0T |
| Descriptor | Cyclic dipeptide N-prenyltransferase, (3S)-3-(1H-indol-3-ylmethyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione, TRIHYDROGEN THIODIPHOSPHATE, ... (7 entities in total) |
| Functional Keywords | pt-fold, c(3)b-prenyltransferase, transferase |
| Biological source | Aspergillus fumigatus |
| Total number of polymer chains | 2 |
| Total formula weight | 98927.45 |
| Authors | Schuller, J.M.,Zocher, G.,Stehle, T. (deposition date: 2012-03-05, release date: 2012-05-30, Last modification date: 2023-09-13) |
| Primary citation | Schuller, J.M.,Zocher, G.,Liebhold, M.,Xie, X.,Stahl, M.,Li, S.M.,Stehle, T. Structure and catalytic mechanism of a cyclic dipeptide prenyltransferase with broad substrate promiscuity. J.Mol.Biol., 422:87-99, 2012 Cited by PubMed Abstract: Fungal indole prenyltransferases (PTs) typically act on specific substrates, and they are able to prenylate their target compounds with remarkably high regio- and stereoselectivity. Similar to several indole PTs characterized to date, the cyclic dipeptide N-prenyltransferase (CdpNPT) is able to prenylate a range of diverse substrates, thus exhibiting an unusually broad substrate promiscuity. To define the structural basis for this promiscuity, we have determined crystal structures of unliganded CdpNPT and of a ternary complex of CdpNPT bound to (S)-benzodiazepinedione and thiolodiphosphate. Analysis of the structures reveals a limited number of specific interactions with (S)-benzodiazepinedione, which projects into a largely hydrophobic surface. This surface can also accommodate other substrates, explaining the ability of the enzyme to prenylate a range of compounds. The location of the bound substrates suggests a likely reaction mechanism for the conversion of (S)-benzodiazepinedione. Structure-guided mutagenesis experiments confirm that, in addition to (S)-benzodiazepinedione, CdpNPT can also act on (R)-benzodiazepinedione and several cyclic dipeptides, albeit with relaxed specificity. Finally, nuclear magnetic resonance spectroscopy demonstrates that CdpNPT is a C-3 reverse PT that catalyzes the formation of C-3β prenylated indolines from diketopiperazines of tryptophan-containing cyclic dipeptides. PubMed: 22683356DOI: 10.1016/j.jmb.2012.05.033 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.6 Å) |
Structure validation
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