6ag4: Difference between revisions

From Proteopedia
Jump to navigation Jump to search
← Older edit
No edit summary
No edit summary
 
(One intermediate revision by the same user not shown)
Line 3: Line 3:
<StructureSection load='6ag4' size='340' side='right'caption='[[6ag4]], [[Resolution|resolution]] 2.26&Aring;' scene=''>
<StructureSection load='6ag4' size='340' side='right'caption='[[6ag4]], [[Resolution|resolution]] 2.26&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6ag4]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AG4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AG4 FirstGlance]. <br>
<table><tr><td colspan='2'>[[6ag4]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharolobus_solfataricus_P2 Saccharolobus solfataricus P2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AG4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6AG4 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACO:ACETYL+COENZYME+*A'>ACO</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.256&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ag4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ag4 OCA], [http://pdbe.org/6ag4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ag4 RCSB], [http://www.ebi.ac.uk/pdbsum/6ag4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ag4 ProSAT]</span></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACO:ACETYL+COENZYME+*A'>ACO</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=6ag4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ag4 OCA], [https://pdbe.org/6ag4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ag4 RCSB], [https://www.ebi.ac.uk/pdbsum/6ag4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ag4 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
[https://www.uniprot.org/uniprot/NAT_SACS2 NAT_SACS2] Displays alpha (N-terminal) acetyltransferase activity. Catalyzes the covalent attachment of an acetyl moiety from acetyl-CoA to the free alpha-amino group at the N-terminus of a protein (PubMed:17511810, PubMed:23959863, PubMed:25728374). NAT is able to acetylate the alpha-amino group of methionine, alanine and serine N-terminal residue substrates, however it has a preference for Ser-N-terminal substrates (PubMed:17511810, PubMed:23959863, PubMed:25728374).<ref>PMID:17511810</ref> <ref>PMID:23959863</ref> <ref>PMID:25728374</ref>
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
Nalpha-acetyltransferases (Nats) possess a wide range of important biological functions. Their structures can vary according to the first two residues of their substrate. However, the mechanisms of substrate recognition and catalysis of Nats are elusive. Here, we present two structure of Sulfolobus solfataricus Ard1 (SsArd1), a member of the NatA family, at 2.13 and 1.84 A. Both structures contain coenzyme A, while the latter also contains a substrate-derived peptide. Sequential structure-based mutagenesis revealed that mutations of critical residues for CoA binding decreased the binding affinity of SsArd1 by 3 ~ 7-fold. Superimposition of SsArd1 (NatA) with human Naa50p (NatE) showed significant differences in key residues of enzymes near the first amino-acid position of the substrate peptide (Glu35 for SsArd1 and Val29 for Naa50p). Further enzyme activity assays revealed that the substrate specificity of SsArd1 could be altered from SSGTPT to MEEKVG by a range of Glu35 mutants. These studies provide not only a molecular elucidation of substrate recognition and specificity for the NatA family, but also insight into how members of the NAT family distinguish between amino acids at the substrate N-terminus from the ancient monomeric archaeal Ard1.
The common mechanism of N-acetyltransferases (NATs) is a water-mediated catalysis, which is not conducive to thermophilic acetyltransferases. The crystal structure of SsArd1 shows an ordered catalytic water molecule in a trap formed by the residues H88 and E127. Structure-guided mutagenesis, kinetic studies and MD simulation indicated that the turnover rates of H88A, E127A and H88A/E127A mutants were low, but that of the H88E/E127H mutant could be restored to the level of the wild type.


Structural Basis for Substrate-specific Acetylation of Nalpha-acetyltransferase Ard1 from Sulfolobus solfataricus.,Chang YY, Hsu CH Sci Rep. 2015 Mar 2;5:8673. doi: 10.1038/srep08673. PMID:25728374<ref>PMID:25728374</ref>
Adaptation of thermophilic acetyltransferase to a water-mediated catalytic mechanism.,Chang YY, Hagawa S, Hsu CH Chem Commun (Camb). 2020 Sep 10;56(72):10537-10540. doi: 10.1039/d0cc04305b. PMID:32780067<ref>PMID:32780067</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
Line 21: Line 24:
</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Chang, Y Y]]
[[Category: Saccharolobus solfataricus P2]]
[[Category: Hsu, C H]]
[[Category: Chang YY]]
[[Category: Acetyltransferase]]
[[Category: Hsu CH]]
[[Category: Transferase]]

Latest revision as of 12:30, 22 November 2023

Crystal structure of Ard1 N-terminal acetyltransferase H88A/E127A mutant from Sulfolobus solfataricusCrystal structure of Ard1 N-terminal acetyltransferase H88A/E127A mutant from Sulfolobus solfataricus

Structural highlights

6ag4 is a 1 chain structure with sequence from Saccharolobus solfataricus P2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.256Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

NAT_SACS2 Displays alpha (N-terminal) acetyltransferase activity. Catalyzes the covalent attachment of an acetyl moiety from acetyl-CoA to the free alpha-amino group at the N-terminus of a protein (PubMed:17511810, PubMed:23959863, PubMed:25728374). NAT is able to acetylate the alpha-amino group of methionine, alanine and serine N-terminal residue substrates, however it has a preference for Ser-N-terminal substrates (PubMed:17511810, PubMed:23959863, PubMed:25728374).[1] [2] [3]

Publication Abstract from PubMed

The common mechanism of N-acetyltransferases (NATs) is a water-mediated catalysis, which is not conducive to thermophilic acetyltransferases. The crystal structure of SsArd1 shows an ordered catalytic water molecule in a trap formed by the residues H88 and E127. Structure-guided mutagenesis, kinetic studies and MD simulation indicated that the turnover rates of H88A, E127A and H88A/E127A mutants were low, but that of the H88E/E127H mutant could be restored to the level of the wild type.

Adaptation of thermophilic acetyltransferase to a water-mediated catalytic mechanism.,Chang YY, Hagawa S, Hsu CH Chem Commun (Camb). 2020 Sep 10;56(72):10537-10540. doi: 10.1039/d0cc04305b. PMID:32780067[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. ↑ Mackay DT, Botting CH, Taylor GL, White MF. An acetylase with relaxed specificity catalyses protein N-terminal acetylation in Sulfolobus solfataricus. Mol Microbiol. 2007 Jun;64(6):1540-8. doi: 10.1111/j.1365-2958.2007.05752.x. Epub , 2007 May 18. PMID:17511810 doi:http://dx.doi.org/10.1111/j.1365-2958.2007.05752.x
  2. ↑ Liszczak G, Marmorstein R. Implications for the evolution of eukaryotic amino-terminal acetyltransferase (NAT) enzymes from the structure of an archaeal ortholog. Proc Natl Acad Sci U S A. 2013 Sep 3;110(36):14652-7. doi:, 10.1073/pnas.1310365110. Epub 2013 Aug 19. PMID:23959863 doi:http://dx.doi.org/10.1073/pnas.1310365110
  3. ↑ Chang YY, Hsu CH. Structural Basis for Substrate-specific Acetylation of Nalpha-acetyltransferase Ard1 from Sulfolobus solfataricus. Sci Rep. 2015 Mar 2;5:8673. doi: 10.1038/srep08673. PMID:25728374 doi:http://dx.doi.org/10.1038/srep08673
  4. ↑ Chang YY, Hagawa S, Hsu CH. Adaptation of thermophilic acetyltransferase to a water-mediated catalytic mechanism. Chem Commun (Camb). 2020 Sep 10;56(72):10537-10540. doi: 10.1039/d0cc04305b. PMID:32780067 doi:http://dx.doi.org/10.1039/d0cc04305b

6ag4, resolution 2.26Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA
Retrieved from "https://proteopedia.openfox.io/wiki/index.php?title=6ag4&oldid=3958772"