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| {{STRUCTURE_2ref| PDB=2ref | SCENE= }} | | {{STRUCTURE_2ref| PDB=2ref | SCENE= }} |
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| '''Crystal structure of the loading GNATL domain of CurA from Lyngbya majuscula soaked with malonyl-CoA'''
| | ===Crystal structure of the loading GNATL domain of CurA from Lyngbya majuscula soaked with malonyl-CoA=== |
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| ==Overview==
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| An unexpected biochemical strategy for chain initiation is described for the loading module of the polyketide synthase of curacin A, an anticancer lead derived from the marine cyanobacterium Lyngbya majuscula. A central GCN5-related N-acetyltransferase (GNAT) domain bears bifunctional decarboxylase/S-acetyltransferase activity, both unprecedented for the GNAT superfamily. A CurA loading tridomain, consisting of an adaptor domain, the GNAT domain, and an acyl carrier protein, was assessed biochemically, revealing that a domain showing homology to GNAT (GNAT(L)) catalyzes (i) decarboxylation of malonyl-coenzyme A (malonyl-CoA) to acetyl-CoA and (ii) direct S-acetyl transfer from acetyl-CoA to load an adjacent acyl carrier protein domain (ACP(L)). Moreover, the N-terminal adapter domain was shown to facilitate acetyl-group transfer. Crystal structures of GNAT(L) were solved at 1.95 angstroms (ligand-free form) and 2.75 angstroms (acyl-CoA complex), showing distinct substrate tunnels for acyl-CoA and holo-ACP(L) binding. Modeling and site-directed mutagenesis experiments demonstrated that histidine-389 and threonine-355, at the convergence of the CoA and ACP tunnels, participate in malonyl-CoA decarboxylation but not in acetyl-group transfer. Decarboxylation precedes acetyl-group transfer, leading to acetyl-ACP(L) as the key curacin A starter unit.
| | The line below this paragraph, {{ABSTRACT_PUBMED_17991863}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 17991863 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_17991863}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: S-acetyltransferase]] | | [[Category: S-acetyltransferase]] |
| [[Category: Transferase]] | | [[Category: Transferase]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 16:44:39 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 00:57:18 2008'' |
