3a2b
Crystal Structure of Serine Palmitoyltransferase from Sphingobacterium multivorum with substrate L-serine
Structural highlights
FunctionSPT_SPHMU Catalyzes the condensation of L-serine with palmitoyl-CoA (hexadecanoyl-CoA) to produce 3-oxosphinganine (PubMed:17557831). Exhibits a broad substrate specificity concerning the chain length and the degree of unsaturation of acyl-CoA (PubMed:17557831).[1] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedSerine palmitoyltransferase (SPT) is a key enzyme of sphingolipid biosynthesis and catalyses the pyridoxal 5'-phosphate (PLP)-dependent decarboxylative condensation reaction of l-serine with palmitoyl-CoA to generate 3-ketodihydrosphingosine. The crystal structure of SPT from Sphingobacterium multivorum GTC97 complexed with l-serine was determined at 2.3 A resolution. The electron density map showed the Schiff base formation between l-serine and PLP in the crystal. Because of the hydrogen bond formation with His138, the orientation of the Calpha-H bond of the PLP-l-serine aldimine was not perpendicular to the PLP-Schiff base plane. This conformation is unfavourable for the alpha-proton abstraction by Lys244 and the reaction is expected to stop at the PLP-l-serine aldimine. Structural modelling of the following intermediates indicated that His138 changes its hydrogen bond partner from the carboxyl group of l-serine to the carbonyl group of palmitoyl-CoA upon the binding of palmitoyl-CoA, making the l-serine Calpha-H bond perpendicular to the PLP-Schiff base plane. These crystal and model structures well explained the observations on bacterial SPTs that the alpha-deprotonation of l-serine occurs only in the presence of palmitoyl-CoA. This study provides the structural evidence that directly supports our proposed mechanism of the substrate synergism in the SPT reaction. Structural insights into the enzymatic mechanism of serine palmitoyltransferase from Sphingobacterium multivorum.,Ikushiro H, Islam MM, Okamoto A, Hoseki J, Murakawa T, Fujii S, Miyahara I, Hayashi H J Biochem. 2009 Oct;146(4):549-62. Epub 2009 Jun 29. PMID:19564159[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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