1V26

Crystal structure of tt0168 from Thermus thermophilus HB8

Summary for 1V26

• Entry DOI: 10.2210/pdb1v26/pdb
• Related: 1V25
• Descriptor: long-chain-fatty-acid-CoA synthetase, MAGNESIUM ION, MYRISTIC ACID, ... (5 entities in total)
• Functional Keywords: ligase, structural genomics, riken structural genomics/proteomics initiative, rsgi
• Biological source: Thermus thermophilus
• Total number of polymer chains: 2
• Total formula weight: 120498.27

Authors

Hisanaga, Y.,Ago, H.,Nakatsu, T.,Hamada, K.,Ida, K.,Kanda, H.,Yamamoto, M.,Hori, T.,Arii, Y.,Sugahara, M.,Kuramitsu, S.,Yokoyama, S.,Miyano, M.,RIKEN Structural Genomics/Proteomics Initiative (RSGI) (deposition date: 2003-10-07, release date: 2004-07-27, Last modification date: 2023-12-27)

Primary citation

Hisanaga, Y.,Ago, H.,Nakagawa, N.,Hamada, K.,Ida, K.,Yamamoto, M.,Hori, T.,Arii, Y.,Sugahara, M.,Kuramitsu, S.,Yokoyama, S.,Miyano, M.
Structural Basis of the Substrate-specific Two-step Catalysis of Long Chain Fatty Acyl-CoA Synthetase Dimer
J.Biol.Chem., 279:31717-31726, 2004

PubMed Abstract: Long chain fatty acyl-CoA synthetases are responsible for fatty acid degradation as well as physiological regulation of cellular functions via the production of long chain fatty acyl-CoA esters. We report the first crystal structures of long chain fatty acyl-CoA synthetase homodimer (LC-FACS) from Thermus thermophilus HB8 (ttLC-FACS), including complexes with the ATP analogue adenosine 5'-(beta,gamma-imido) triphosphate (AMP-PNP) and myristoyl-AMP. ttLC-FACS is a member of the adenylate forming enzyme superfamily that catalyzes the ATP-dependent acylation of fatty acid in a two-step reaction. The first reaction step was shown to propagate in AMP-PNP complex crystals soaked with myristate solution. Myristoyl-AMP was identified as the intermediate. The AMP-PNP and the myristoyl-AMP complex structures show an identical closed conformation of the small C-terminal domains, whereas the uncomplexed form shows a variety of open conformations. Upon ATP binding, the fatty acid-binding tunnel gated by an aromatic residue opens to the ATP-binding site. The gated fatty acid-binding tunnel appears only to allow one-way movement of the fatty acid during overall catalysis. The protein incorporates a hydrophobic branch from the fatty acid-binding tunnel that is responsible for substrate specificity. Based on these high resolution crystal structures, we propose a unidirectional Bi Uni Uni Bi Ping-Pong mechanism for the two-step acylation by ttLC-FACS.

PubMed: 15145952
DOI: 10.1074/jbc.M400100200

Experimental method

X-RAY DIFFRACTION (2.5 Å)