Supplementary material to
N-terminal N-Myristoylation of Proteins:
I. Refinement of the Sequence Motif and its Taxon-specific Differences
II. Prediction of Substrate Proteins from Amino Acid Sequence
Sebastian Maurer-StrohBirgit Eisenhaber
Research Institute of Molecular Pathology (IMP),
Dr. Bohr-Gasse 7,
A - 1030 Vienna, Austria
Fax: +43 1 7987153
Myristoylation is a very important lipid modification at the N-terminus of eukaryotic and viral proteins. It is involved in directing and anchoring proteins to membranes and, as a consequence, cellular regulation, signal transduction, translocation, several viral induced pathological processes and even apoptosis. The enzyme myristoylCoA:protein N-myristoyltransferase (NMT) recognizes certain characteristics within the N-termini of substrate proteins and finally attaches the lipid moiety to a required N-terminal glycine.
By analysis of known substrate protein sequences and kinetic data, we refined the motif for N-terminal (glycine) myristoylation and identified three motif regions: region 1 (positions 1-6) fitting the binding pocket, region 2 (positions 7-10) interacting with the NMT's surface at the mouth of the catalytic cavity, and region 3 (positions 11-17) comprising a hydrophilic linker. Each region was characterized by specific requirements concerning volume compensations, polarity, flexibility parameters and other typical properties of amino acid side chains. Additionally, evolutionary shifts between lower and higher eukaryotic NMT sequences were observed. This differences were used to shed light on the taxon-specific substrate preferences and, furthermore, lead to suggestions for the construction of selective inhibitors against various pathogenic fungi and protozoa.
List of proteins who are substrates to NMT.
1. Alignment of the 21 NMTs in NR database (plus 2 potential NMTs from entomopoxviri)
2. Complete alignment (including ESTs) of sequences homologous to experimentally characterized NMTs from 64 different organisms.
Phylogenetic trees of NMTs from various taxa.
Download our models, Interactive comparison of fungal and human
NMT (requires CHIME), MPEG-movie of a virtual flight through
the NMT binding pocket.
Online submission of Your query sequence.
Lists of predicted proteins (including learning set sequences to show self-consistency) within SWISSPROT 40.2 (2.11.2001). According to our parameter sets we divide into fungi and eukaryota (without fungi) plus viruses.
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