Enzymes
| UniProtKB help_outline | 3 proteins |
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Namehelp_outline
N-terminal L-aspartyl-L-aspartyl-L-aspartyl-[protein]
Identifier
RHEA-COMP:14863
Reactive part
help_outline
- Name help_outline N-terminal L-Asp-L-Asp-L-Asp residue Identifier CHEBI:141602 Charge -2 Formula C12H14N3O9 SMILEShelp_outline [NH3+][C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)*)CC(=O)[O-])CC(=O)[O-])CC(=O)[O-] 2D coordinates Mol file for the small molecule Search links Involved in 1 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline acetyl-CoA Identifier CHEBI:57288 (Beilstein: 8468140) help_outline Charge -4 Formula C23H34N7O17P3S InChIKeyhelp_outline ZSLZBFCDCINBPY-ZSJPKINUSA-J SMILEShelp_outline CC(=O)SCCNC(=O)CCNC(=O)[C@H](O)C(C)(C)COP([O-])(=O)OP([O-])(=O)OC[C@H]1O[C@H]([C@H](O)[C@@H]1OP([O-])([O-])=O)n1cnc2c(N)ncnc12 2D coordinates Mol file for the small molecule Search links Involved in 361 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
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Namehelp_outline
N-terminal N-acetyl-L-aspartyl-L-aspartyl-L-aspartyl-[protein]
Identifier
RHEA-COMP:14864
Reactive part
help_outline
- Name help_outline N-terminal N-acetyl-L-Asp-L-Asp-L-Asp residue Identifier CHEBI:141604 Charge -3 Formula C14H15N3O10 SMILEShelp_outline N([C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)*)CC(=O)[O-])CC(=O)[O-])CC(=O)[O-])C(C)=O 2D coordinates Mol file for the small molecule Search links Involved in 1 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline CoA Identifier CHEBI:57287 (Beilstein: 11604429) help_outline Charge -4 Formula C21H32N7O16P3S InChIKeyhelp_outline RGJOEKWQDUBAIZ-IBOSZNHHSA-J SMILEShelp_outline CC(C)(COP([O-])(=O)OP([O-])(=O)OC[C@H]1O[C@H]([C@H](O)[C@@H]1OP([O-])([O-])=O)n1cnc2c(N)ncnc12)[C@@H](O)C(=O)NCCC(=O)NCCS 2D coordinates Mol file for the small molecule Search links Involved in 1,511 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H+ Identifier CHEBI:15378 Charge 1 Formula H InChIKeyhelp_outline GPRLSGONYQIRFK-UHFFFAOYSA-N SMILEShelp_outline [H+] 2D coordinates Mol file for the small molecule Search links Involved in 9,521 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
| RHEA:57328 | RHEA:57329 | RHEA:57330 | RHEA:57331 | |
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| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
| UniProtKB help_outline |
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| MetaCyc help_outline |
Related reactions help_outline
More general form(s) of this reaction
Publications
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NAA80 is actin's N-terminal acetyltransferase and regulates cytoskeleton assembly and cell motility.
Drazic A., Aksnes H., Marie M., Boczkowska M., Varland S., Timmerman E., Foyn H., Glomnes N., Rebowski G., Impens F., Gevaert K., Dominguez R., Arnesen T.
Actin, one of the most abundant proteins in nature, participates in countless cellular functions ranging from organelle trafficking and pathogen motility to cell migration and regulation of gene transcription. Actin's cellular activities depend on the dynamic transition between its monomeric and f ... >> More
Actin, one of the most abundant proteins in nature, participates in countless cellular functions ranging from organelle trafficking and pathogen motility to cell migration and regulation of gene transcription. Actin's cellular activities depend on the dynamic transition between its monomeric and filamentous forms, a process exquisitely regulated in cells by a large number of actin-binding and signaling proteins. Additionally, several posttranslational modifications control the cellular functions of actin, including most notably N-terminal (Nt)-acetylation, a prevalent modification throughout the animal kingdom. However, the biological role and mechanism of actin Nt-acetylation are poorly understood, and the identity of actin's N-terminal acetyltransferase (NAT) has remained a mystery. Here, we reveal that NAA80, a suggested NAT enzyme whose substrate specificity had not been characterized, is Nt-acetylating actin. We further show that actin Nt-acetylation plays crucial roles in cytoskeletal assembly in vitro and in cells. The absence of Nt-acetylation leads to significant differences in the rates of actin filament depolymerization and elongation, including elongation driven by formins, whereas filament nucleation by the Arp2/3 complex is mostly unaffected. <i>NAA80</i>-knockout cells display severely altered cytoskeletal organization, including an increase in the ratio of filamentous to globular actin, increased filopodia and lamellipodia formation, and accelerated cell motility. Together, the results demonstrate NAA80's role as actin's NAT and reveal a crucial role for actin Nt-acetylation in the control of cytoskeleton structure and dynamics. << Less
Proc. Natl. Acad. Sci. U.S.A. 115:4399-4404(2018) [PubMed] [EuropePMC]
This publication is cited by 2 other entries.
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Structural determinants and cellular environment define processed actin as the sole substrate of the N-terminal acetyltransferase NAA80.
Goris M., Magin R.S., Foyn H., Myklebust L.M., Varland S., Ree R., Drazic A., Bhambra P., Stoeve S.I., Baumann M., Haug B.E., Marmorstein R., Arnesen T.
N-terminal (Nt) acetylation is a major protein modification catalyzed by N-terminal acetyltransferases (NATs). Methionine acidic N termini, including actin, are cotranslationally Nt acetylated by NatB in all eukaryotes, but animal actins containing acidic N termini, are additionally posttranslatio ... >> More
N-terminal (Nt) acetylation is a major protein modification catalyzed by N-terminal acetyltransferases (NATs). Methionine acidic N termini, including actin, are cotranslationally Nt acetylated by NatB in all eukaryotes, but animal actins containing acidic N termini, are additionally posttranslationally Nt acetylated by NAA80. Actin Nt acetylation was found to regulate cytoskeletal dynamics and motility, thus making NAA80 a potential target for cell migration regulation. In this work, we developed potent and selective bisubstrate inhibitors for NAA80 and determined the crystal structure of NAA80 in complex with such an inhibitor, revealing that NAA80 adopts a fold similar to other NAT enzymes but with a more open substrate binding region. Furthermore, in contrast to most other NATs, the substrate specificity of NAA80 is mainly derived through interactions between the enzyme and the acidic amino acids at positions 2 and 3 of the actin substrate and not residues 1 and 2. A yeast model revealed that ectopic expression of NAA80 in a strain lacking NatB activity partially restored Nt acetylation of NatB substrates, including yeast actin. Thus, NAA80 holds intrinsic capacity to posttranslationally Nt acetylate NatB-type substrates in vivo. In sum, the presence of a dominant cotranslational NatB in all eukaryotes, the specific posttranslational actin methionine removal in animals, and finally, the unique structural features of NAA80 leave only the processed actins as in vivo substrates of NAA80. Together, this study reveals the molecular and cellular basis of NAA80 Nt acetylation and provides a scaffold for development of inhibitors for the regulation of cytoskeletal properties. << Less
Proc. Natl. Acad. Sci. U.S.A. 115:4405-4410(2018) [PubMed] [EuropePMC]
This publication is cited by 2 other entries.