4YL5

Structure of a putative phosphomethylpyrimidine kinase from Acinetobacter baumannii

4YL5 の概要

• エントリーDOI: 10.2210/pdb4yl5/pdb
• 分子名称: Putative phosphomethylpyrimidine kinase, 1,2-ETHANEDIOL (3 entities in total)
• 機能のキーワード: putative phosphomethylpyrimidine kinase, structural genomics, seattle structural genomics center for infectious disease, ssgcid, transferase
• 由来する生物種: Acinetobacter baumannii IS-123
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 27854.73

構造登録者

Seattle Structural Genomics Center for Infectious Disease (SSGCID) (登録日: 2015-03-04, 公開日: 2015-04-01, 最終更新日: 2024-11-06)

主引用文献

De Vitto, H.,Belfon, K.K.J.,Sharma, N.,Toay, S.,Abendroth, J.,Dranow, D.M.,Lukacs, C.M.,Choi, R.,Udell, H.S.,Willis, S.,Barrera, G.,Beyer, O.,Li, T.D.,Hicks, K.A.,Torelli, A.T.,French, J.B.
Characterization of an Acinetobacter baumannii Monofunctional Phosphomethylpyrimidine Kinase That Is Inhibited by Pyridoxal Phosphate.
Biochemistry, 2024

PubMed Abstract: Thiamin and its phosphate derivatives are ubiquitous molecules involved as essential cofactors in many cellular processes. The biosynthesis of thiamin employs the parallel synthesis of 4-methyl-5-(2-hydroxyethyl)thiazole (THZ-P) and 4-amino-2-methyl-5(diphosphooxymethyl) pyrimidine (HMP) pyrophosphate (HMP-PP), which are coupled to generate thiamin phosphate. Most organisms that can biosynthesize thiamin employ a kinase (HMPK or ThiD) to generate HMP-PP. In nearly all cases, this enzyme is bifunctional and can also salvage free HMP, producing HMP-P, the monophosphate precursor of HMP-PP. Here we present high-resolution crystal structures of an HMPK from (AbHMPK), both unliganded and with pyridoxal 5-phosphate (PLP) noncovalently bound. Despite the similarity between HMPK and pyridoxal kinase enzymes, our kinetics analysis indicates that AbHMPK accepts HMP exclusively as a substrate and cannot turn over pyridoxal, pyridoxamine, or pyridoxine nor does it display phosphatase activity. PLP does, however, act as a weak inhibitor of AbHMPK with an IC of 768 μM. Surprisingly, unlike other HMPKs, AbHMPK catalyzes only the phosphorylation of HMP and does not generate the diphosphate HMP-PP. This suggests that an additional kinase is present in , or an alternative mechanism is in operation to complete the biosynthesis of thiamin.

PubMed: 38306231
DOI: 10.1021/acs.biochem.3c00640

実験手法

X-RAY DIFFRACTION (1.7 Å)