2ref
From Proteopedia
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| - | [[Image:2ref.jpg|left|200px]] | + | [[Image:2ref.jpg|left|200px]] |
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| - | '''Crystal structure of the loading GNATL domain of CurA from Lyngbya majuscula soaked with malonyl-CoA''' | + | {{Structure |
| + | |PDB= 2ref |SIZE=350|CAPTION= <scene name='initialview01'>2ref</scene>, resolution 2.750Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=ACO:ACETYL COENZYME *A'>ACO</scene> | ||
| + | |ACTIVITY= | ||
| + | |GENE= curA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=158786 Lyngbya majuscula]) | ||
| + | }} | ||
| + | |||
| + | '''Crystal structure of the loading GNATL domain of CurA from Lyngbya majuscula soaked with malonyl-CoA''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2REF is a [ | + | 2REF is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Lyngbya_majuscula Lyngbya majuscula]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2REF OCA]. |
==Reference== | ==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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/17991863 17991863] |
[[Category: Lyngbya majuscula]] | [[Category: Lyngbya majuscula]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:35:17 2008'' |
Revision as of 16:35, 20 March 2008
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| , resolution 2.750Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | curA (Lyngbya majuscula) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of the loading GNATL domain of CurA from Lyngbya majuscula soaked with malonyl-CoA
Overview
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.
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
Page seeded by OCA on Thu Mar 20 18:35:17 2008
