2B3V

Spermine spermidine acetyltransferase in complex with acetylcoa, K26R mutant

2B3V の概要

• エントリーDOI: 10.2210/pdb2b3v/pdb
• 関連するPDBエントリー: 2B3U 2B47 2B4B 2B4D 2B5G
• 分子名称: Diamine acetyltransferase 1, ACETYL COENZYME *A (3 entities in total)
• 機能のキーワード: polyamine, structural genomics, psi, protein structure initiative, new york sgx research center for structural genomics, nysgxrc, transferase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 21213.84

構造登録者

Bewley, M.C.,Graziano, V.,Jiang, J.S.,Matz, E.,Studier, F.W.,Pegg, A.P.,Coleman, C.S.,Flanagan, J.M.,Burley, S.K.,New York SGX Research Center for Structural Genomics (NYSGXRC) (登録日: 2005-09-21, 公開日: 2006-01-17, 最終更新日: 2024-10-30)

主引用文献

Bewley, M.C.,Graziano, V.,Jiang, J.,Matz, E.,Studier, F.W.,Pegg, A.E.,Coleman, C.S.,Flanagan, J.M.
Structures of wild-type and mutant human spermidine/spermine N1-acetyltransferase, a potential therapeutic drug target.
Proc.Natl.Acad.Sci.USA, 103:2063-2068, 2006

PubMed Abstract: Spermidine/spermine N1-acetyltransferase (SSAT) is a key enzyme in the control of polyamine levels in human cells, as acetylation of spermidine and spermine triggers export or degradation. Increased intracellular polyamine levels accompany several types of cancers as well as other human diseases, and compounds that affect the expression, activity, or stability of SSAT are being explored as potential therapeutic drugs. We have expressed human SSAT from the cloned cDNA in Escherichia coli and have determined high-resolution structures of wild-type and mutant SSAT, as the free dimer and in binary and ternary complexes with CoA, acetyl-CoA (AcCoA), spermine, and the inhibitor N1,N11bis-(ethyl)-norspermine (BE-3-3-3). These structures show details of binding sites for cofactor, substrates, and inhibitor and provide a framework to understand enzymatic activity, mutations, and the action of potential drugs. Two dimer conformations were observed: a symmetric form with two open surface channels capable of binding substrate or cofactor, and an asymmetric form in which only one of the surface channels appears capable of binding and acetylating polyamines. SSAT was found to self-acetylate lysine-26 in the presence of AcCoA and absence of substrate, a reaction apparently catalzyed by AcCoA bound in the second channel of the asymmetric dimer. These unexpected and intriguing complexities seem likely to have some as yet undefined role in regulating SSAT activity or stability as a part of polyamine homeostasis. Sequence signatures group SSAT with proteins that appear to have thialysine Nepsilon-acetyltransferase activity.

PubMed: 16455797
DOI: 10.1073/pnas.0511008103

実験手法

X-RAY DIFFRACTION (1.95 Å)