4j1s

From Proteopedia

Crystal structure of a ketoreductase domain from the bacillaene assembly line

Structural highlights

4j1s is a 1 chain structure with sequence from Bacillus subtilis subsp. subtilis str. 168. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.01Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PKSJ_BACSU Involved in some intermediate steps for the synthesis of the antibiotic polyketide bacillaene which is involved in secondary metabolism.^[1] ^[2]

Publication Abstract from PubMed

While the cis-acyltransferase modular polyketide synthase assembly lines have largely been structurally dissected, enzymes from within the recently discovered trans-acyltransferase polyketide synthase assembly lines are just starting to be observed crystallographically. Here we examine the ketoreductase (KR) from the first polyketide synthase module of the bacillaene nonribosomal peptide synthetase/polyketide synthase at 2.35-A resolution. This KR naturally reduces both alpha- and beta-keto groups and is the only KR known to do so during the biosynthesis of a polyketide. The isolated KR not only reduced an N-acetylcysteamine-bound beta-keto substrate to a D-beta-hydroxy product, but also an N-acetylcysteamine-bound alpha-keto substrate to an L-alpha-hydroxy product. That the substrates must enter the active site from opposite directions to generate these stereochemistries suggests that the acyl-phosphopantetheine moiety is capable of accessing very different conformations despite being anchored to a serine residue of a docked acyl carrier protein. The features enabling stereocontrolled alpha-ketoreduction may not be extensive since a KR that naturally reduces a beta-keto group within a cis-acyltransferase polyketide synthase was identified that performs a completely stereoselective reduction of the same alpha-keto substrate to generate the D-alpha-hydroxy product. A sequence analysis of trans-acyltransferase KRs reveals that a single residue, rather than a three-residue motif found in cis-acyltransferase KRs, is predictive of the orientation of the resulting beta-hydroxyl group.Proteins 2014. (c) 2014 Wiley Periodicals, Inc.

Structural and functional studies of a trans-acyltransferase polyketide assembly line enzyme that catalyzes stereoselective alpha- and beta-ketoreduction.,Piasecki SK, Zheng J, Axelrod AJ, E Detelich M, Keatinge-Clay AT Proteins. 2014 Mar 14. doi: 10.1002/prot.24561. PMID:24634061^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Dorrestein PC, Blackhall J, Straight PD, Fischbach MA, Garneau-Tsodikova S, Edwards DJ, McLaughlin S, Lin M, Gerwick WH, Kolter R, Walsh CT, Kelleher NL. Activity screening of carrier domains within nonribosomal peptide synthetases using complex substrate mixtures and large molecule mass spectrometry. Biochemistry. 2006 Feb 14;45(6):1537-46. PMID:16460000 doi:http://dx.doi.org/10.1021/bi052333k
↑ Butcher RA, Schroeder FC, Fischbach MA, Straight PD, Kolter R, Walsh CT, Clardy J. The identification of bacillaene, the product of the PksX megacomplex in Bacillus subtilis. Proc Natl Acad Sci U S A. 2007 Jan 30;104(5):1506-9. Epub 2007 Jan 18. PMID:17234808 doi:http://dx.doi.org/10.1073/pnas.0610503104
↑ Piasecki SK, Zheng J, Axelrod AJ, E Detelich M, Keatinge-Clay AT. Structural and functional studies of a trans-acyltransferase polyketide assembly line enzyme that catalyzes stereoselective alpha- and beta-ketoreduction. Proteins. 2014 Mar 14. doi: 10.1002/prot.24561. PMID:24634061 doi:http://dx.doi.org/10.1002/prot.24561