1wlu | pdb_00001wlu
Crystal structure of TT0310 protein from Thermus thermophilus HB8
|
Overview
Hot dog fold proteins sharing the characteristic "hot dog" fold are known, to involve certain coenzyme A binding enzymes with various oligomeric, states. In order to elucidate the oligomerization-function relationship of, the hot dog fold proteins, crystal structures of the phenylacetate, degradation protein PaaI from Thermus thermophilus HB8 (TtPaaI), a, tetrameric acyl-CoA thioesterase with the hot dog fold, have been, determined and compared with those of other family members. In the, liganded crystal forms with coenzyme A derivatives, only two of four, intersubunit catalytic pockets of the TtPaaI tetramer are occupied by the, ligands. A detailed structural comparison between several liganded and, unliganded forms reveals that a subtle rigid-body rearrangement of, subunits within 2 degrees upon binding of the first two ligand molecules, can induce a strict negative cooperativity to prevent further binding at, the remaining two pockets, indicating that the so-called, "half-of-the-sites reactivity" of oligomeric enzymes is visualized for the, first time. Considering kinetic and mutational analyses together, a, possible reaction mechanism of TtPaaI is proposed; one tetramer binds only, two acyl-CoA molecules with a novel asymmetric induced-fit mechanism and, carries out the hydrolysis according to a base-catalyzed reaction through, activation of a water molecule by Asp48. From a structural comparison with, other family members, it is concluded that a subgroup of the hot dog fold, protein family, referred to as "asymmetric hot dog thioesterases", including medium chain acyl-CoA thioesterase II from Escherichia coli and, human thioesterase III, might share the same oligomerization mode and the, asymmetric induced-fit mechanism as observed in TtPaaI.
About this Structure
1WLU is a Single protein structure of sequence from Thermus thermophilus with CL and GOL as ligands. Full crystallographic information is available from OCA.
Reference
A novel induced-fit reaction mechanism of asymmetric hot dog thioesterase PAAI., Kunishima N, Asada Y, Sugahara M, Ishijima J, Nodake Y, Sugahara M, Miyano M, Kuramitsu S, Yokoyama S, Sugahara M, J Mol Biol. 2005 Sep 9;352(1):212-28. PMID:16061252
Page seeded by OCA on Sun Nov 25 00:12:27 2007
