Evolutionary trace analysis of N-myristoyltransferase family.
- Author:
Chun-quan SHENG
1
;
Jie ZHU
;
Wan-nian ZHANG
;
Hui XU
;
Zhen-yuan MIAO
;
Jian-zhong YAO
;
Min ZHANG
Author Information
1. School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
- Publication Type:Journal Article
- MeSH:
Acyl Coenzyme A;
metabolism;
Acyltransferases;
chemistry;
genetics;
metabolism;
Amino Acid Sequence;
Animals;
Binding Sites;
Conserved Sequence;
Enzyme Inhibitors;
chemistry;
pharmacology;
Evolution, Molecular;
Humans;
Imidazoles;
chemistry;
pharmacology;
Models, Molecular;
Molecular Sequence Data;
Oligopeptides;
chemistry;
pharmacology;
Phylogeny;
Protein Structure, Tertiary;
Sequence Homology, Amino Acid
- From:
Acta Pharmaceutica Sinica
2007;42(2):157-165
- CountryChina
- Language:Chinese
-
Abstract:
To clarify the important functional residues in the active site of N-myristoyltransferase (NMT), a novel antifungal drug target, and to guide the design of specific inhibitors, multiple sequence alignments were performed on the NMT family and thus evolutionary trace was constructed. The important functional residues in myristoyl CoA binding site, catalytic center and inhibitor binding site of NMT family were identified by ET analysis. The trace residues were mapped onto the active site of CaNMT. Trpl26, Asn175 and Thr211 are highly conserved trace residues and do not interact with current NMT inhibitors, which are potential novel drug binding sites for the novel inhibitor design. Pro338, Leu350, Ile352 and Ala353 are class-specific trace residues, which are important for the optimization of current NMT inhibitors. The trace residues identified by ET analysis are of great importance to study the structure-function relationship and also to guide the design of specific inhibitors.
