1iid | pdb_00001iid

Crystal Structure of Saccharomyces cerevisiae N-myristoyltransferase with Bound S-(2-oxo)pentadecylCoA and the Octapeptide GLYASKLA

spinqualitylabelsall models 1iid, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1iid is a 2 chain structure with sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.5Å Ligands: NHM, NI Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function NMT_YEAST Adds a myristoyl group to the N-terminal glycine residue of certain cellular proteins. Substrate specificity requires an N-terminal glycine in the nascent polypeptide substrates. Uncharged amino acids are preferred at position 2 while neutral residues are favored at positions 3 and 4. Ser is present at position 5 in almost all known N-myristoyl proteins and Lys is commonly encountered at postion 6. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed MyristoylCoA:protein N-myristoyltransferase (Nmt) attaches myristate to the N-terminal Gly residue of proteins involved in a variety of signal transduction cascades, and other critical cellular functions. To gain insight about the structural basis of substrate recognition and catalysis, we determined the structures of a binary complex of Saccharomyces cerevisiae Nmt1p with myristoylCoA to 2.2 A resolution and of a ternary complex of Nmt1p with a nonhydrolyzable myristoylCoA analogue [S-(2-oxo)pentadecylCoA] and an octapeptide substrate (GLYASKLA) to 2.5 A resolution. The binary complex reveals how myristoylCoA alters the conformation of the enzyme to promote binding of both myristoylCoA and peptide and identifies the backbone amides of F170 and L171 as an oxyanion hole which polarizes the reactive thioester carbonyl. The ternary complex structure reveals details of the enzyme's peptide binding specificity and illuminates its mechanism of acyl transfer. The N-terminal Gly ammonium is positioned in close proximity to the C-terminal carboxylate of the protein, where it is poised to undergo the required deprotonation to an amine. In this conformation, the nucleophile is 6.3 A away from the thioester carbonyl. A catalytic mechanism is proposed whereby, once deprotonation is initiated, the N-terminal Gly amine can approximate the thioester carbonyl by rotating along Psi. This motion is facilitated by a H-bond network and leads to reaction between the glycine nitrogen nucleophile and the carbonyl. Loss of CoA from the tetrahedral intermediate may be facilitated by intramolecular H-bonding of the sulfur to the adenylamine of CoA. This affords a compact leaving group and lends a role for the observed bends in the CoA structure. The absolute requirement for Gly at the N-terminus of substrates is explained by the requirement for flexible rotation of its amine. Structures of Saccharomyces cerevisiae N-myristoyltransferase with bound myristoylCoA and peptide provide insights about substrate recognition and catalysis.,Farazi TA, Waksman G, Gordon JI Biochemistry. 2001 May 29;40(21):6335-43. PMID:11371195 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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