790-12-5Relevant articles and documents
Biocatalytic Reversal of Advanced Glycation End Product Modification
Kim, Nam Y.,Goddard, Tyler N.,Sohn, Seungjung,Spiegel, David A.,Crawford, Jason M.
, p. 2402 - 2410 (2019/08/12)
Advanced glycation end products (AGEs) are a heterogeneous group of molecules that emerge from the condensation of sugars and proteins through the Maillard reaction. Despite a significant number of studies showing strong associations between AGEs and the pathologies of aging-related illnesses, it has been a challenge to establish AGEs as causal agents primarily due to the lack of tools in reversing AGE modifications at the molecular level. Herein, we show that MnmC, an enzyme involved in a bacterial tRNA-modification pathway, is capable of reversing the AGEs carboxyethyl-lysine (CEL) and carboxymethyl-lysine (CML) back to their native lysine structure. Combining structural homology analysis, site-directed mutagenesis, and protein domain dissection studies, we generated a variant of MnmC with improved catalytic properties against CEL in its free amino acid form. We show that this enzyme variant is also active on a CEL-modified peptidomimetic and an AGE-containing peptide that has been established as an authentic ligand of the receptor for AGEs (RAGE). Our data demonstrate that MnmC variants are promising lead catalysts toward the development of AGE-reversal tools and a better understanding of AGE biology.
NosA catalyzing carboxyl-terminal amide formation in nosiheptide maturation via an enamine dealkylation on the serine-extended precursor peptide
Yu, Yi,Guo, Heng,Zhang, Qi,Duan, Lian,Ding, Ying,Liao, Rijing,Lei, Chun,Shen, Ben,Liu, Wen
supporting information; experimental part, p. 16324 - 16326 (2011/02/24)
The carboxyl-terminal amide group has been often found in many bioactive peptide natural products, including nosiheptide belonging to the over 80 entity-containing thiopeptide family. Upon functional characterization of a novel protein NosA in nosiheptide biosynthesis, herein we report an unusual C-terminal amide forming strategy in general for maturating certain amide-terminated thiopeptides by processing their precursor peptides featuring a serine extension. NosA acts on an intermediate bearing a bis-dehydroalanine tail and catalyzes an enamide dealkylation to remove the acrylate unit originating from the extended serine residue.
Novel substrate specificity of designer 3-isopropylmalate dehydrogenase derived from Thermus thermophilus HB8
Fujita, Masaaki,Tamegai, Hideyuki,Eguchi, Tadashi,Kakinuma, Katsumi
, p. 2695 - 2700 (2007/10/03)
Redesigning of an enzyme for a new catalytic reaction and modified substrate specificity was exploited with 3-isopropylmalate dehydrogenase (IPMDH). Point-mutation on Gly-89, which is not in the catalytic site but near it, was done by changing it to Ala, Ser, Val, and Pro, and all the mutations changed the substrate specificity. The mutant enzymes showed higher catalytic efficiency (kcat/Km) than the native IPMDH when malate was used as a substrate instead of 3-isopropylmalate. More interestingly, an additional insertion of Gly between Gly-89 and Leu-90 significantly altered the substrate-specificity, although the overall catalytic activity was decreased. Particularly, this mutant turned out to efficiently accept D-lactic acid, which was not accepted as a substrate by wild-type IPMDH at all. These results demonstrate the opportunity for creating novel enzymes by modification of amino acid residues that do not directly participate in catalysis, or by insertion of additional residues.
