1iic: Difference between revisions
No edit summary |
No edit summary |
||
| (10 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
< | ==Crystal Structure of Saccharomyces cerevisiae N-myristoyltransferase with Bound MyristoylCoA== | ||
<StructureSection load='1iic' size='340' side='right'caption='[[1iic]], [[Resolution|resolution]] 2.20Å' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1iic]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IIC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1IIC FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2Å</td></tr> | |||
- | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MYA:TETRADECANOYL-COA'>MYA</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1iic FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1iic OCA], [https://pdbe.org/1iic PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1iic RCSB], [https://www.ebi.ac.uk/pdbsum/1iic PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1iic ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/NMT_YEAST 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 == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ii/1iic_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1iic ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:11371195</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1iic" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | [[Category: Large Structures]] | ||
== | |||
[[Category: | |||
[[Category: Saccharomyces cerevisiae]] | [[Category: Saccharomyces cerevisiae]] | ||
[[Category: Farazi TA]] | |||
[[Category: Farazi | [[Category: Gordon JI]] | ||
[[Category: Gordon | [[Category: Waksman G]] | ||
[[Category: Waksman | |||