Structural highlights
Function
SPT_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]
Publication Abstract from PubMed
Serine palmitoyltransferase (SPT) catalyzes the pyridoxal-5'-phosphate (PLP)-dependent decarboxylative condensation of l-serine and palmitoyl-CoA to form 3-ketodihydrosphingosine (KDS). Although SPT was shown to synthesize corresponding products from amino acids other than l-serine, it is still arguable whether SPT catalyzes the reaction with d-serine, which is a question of biological importance. Using high substrate and enzyme concentrations, KDS was detected after the incubation of SPT from Sphingobacterium multivorum with d-serine and palmitoyl-CoA. Furthermore, the KDS comprised equal amounts of 2S and 2R isomers. (1)H-NMR study showed a slow hydrogen-deuterium exchange at Calpha of serine mediated by SPT. We further confirmed that SPT catalyzed the racemization of serine. The rate of the KDS formation from d-serine was comparable to those for the alpha-hydrogen exchange and the racemization reaction. The structure of the d-serine-soaked crystal (1.65 A resolution) showed a distinct electron density of the PLP-l-serine aldimine, interpreted as the racemized product trapped in the active site. The structure of the alpha-methyl-d-serine-soaked crystal (1.70 A resolution) showed the PLP-alpha-methyl-d-serine aldimine, mimicking the d-serine-SPT complex prior to racemization. Based on these enzymological and structural analyses, the synthesis of KDS from d-serine was explained as the result of the slow racemization to l-serine, followed by the reaction with palmitoyl-CoA, and SPT would not catalyze the direct condensation between d-serine and palmitoyl-CoA. It was also shown that the S. multivorum SPT catalyzed the racemization of the product KDS, which would explain the presence of (2R)-KDS in the reaction products.
Racemization of the substrate and product by serine palmitoyltransferase from Sphingobacterium multivorum yields two enantiomers of the product from d-serine.,Ikushiro H, Honda T, Murai Y, Murakami T, Takahashi A, Sawai T, Goto H, Ikushiro SI, Miyahara I, Hirabayashi Y, Kamiya N, Monde K, Yano T J Biol Chem. 2024 Mar;300(3):105728. doi: 10.1016/j.jbc.2024.105728. Epub 2024 , Feb 5. PMID:38325740[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ikushiro H, Islam MM, Tojo H, Hayashi H. Molecular characterization of membrane-associated soluble serine palmitoyltransferases from Sphingobacterium multivorum and Bdellovibrio stolpii. J Bacteriol. 2007 Aug;189(15):5749-61. PMID:17557831 doi:10.1128/JB.00194-07
- ↑ Ikushiro H, Honda T, Murai Y, Murakami T, Takahashi A, Sawai T, Goto H, Ikushiro SI, Miyahara I, Hirabayashi Y, Kamiya N, Monde K, Yano T. Racemization of the substrate and product by serine palmitoyltransferase from Sphingobacterium multivorum yields two enantiomers of the product from d-serine. J Biol Chem. 2024 Mar;300(3):105728. PMID:38325740 doi:10.1016/j.jbc.2024.105728
