2ref

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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'''
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===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.
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(as it appears on PubMed at http://www.pubmed.gov), where 17991863 is the PubMed ID number.
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{{ABSTRACT_PUBMED_17991863}}
==About this Structure==
==About this Structure==
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[[Category: S-acetyltransferase]]
[[Category: S-acetyltransferase]]
[[Category: Transferase]]
[[Category: Transferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 16:44:39 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 00:57:18 2008''

Revision as of 21:57, 28 July 2008

Template:STRUCTURE 2ref

Crystal structure of the loading GNATL domain of CurA from Lyngbya majuscula soaked with malonyl-CoA

Template:ABSTRACT PUBMED 17991863

About this Structure

2REF is a Single protein structure of sequence from Lyngbya majuscula. Full crystallographic information is available from OCA.

Reference

GNAT-like strategy for polyketide chain initiation., Gu L, Geders TW, Wang B, Gerwick WH, Hakansson K, Smith JL, Sherman DH, Science. 2007 Nov 9;318(5852):970-4. PMID:17991863

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