1V7L

Structure of 3-isopropylmalate isomerase small subunit from Pyrococcus horikoshii

Summary for 1V7L

• Entry DOI: 10.2210/pdb1v7l/pdb
• Descriptor: 3-isopropylmalate dehydratase small subunit (2 entities in total)
• Functional Keywords: beta barrel, lyase
• Biological source: Pyrococcus horikoshii
• Total number of polymer chains: 2
• Total formula weight: 36067.56

Authors

Yao, M.,Kirita, T.,Sakai, N.,Tanaka, I. (deposition date: 2003-12-18, release date: 2004-11-16, Last modification date: 2024-11-13)

Primary citation

Yasutake, Y.,Yao, M.,Sakai, N.,Kirita, T.,Tanaka, I.
Crystal Structure of the Pyrococcus horikoshii Isopropylmalate Isomerase Small Subunit Provides Insight into the Dual Substrate Specificity of the Enzyme
J.Mol.Biol., 344:325-333, 2004

PubMed Abstract: Recent studies have implied that the isopropylmalate isomerase small subunit of the hyperthermophilic archaea Pyrococcus horikoshii (PhIPMI-s) functions as isopropylmalate isomerase in the leucine biosynthesis pathway, and as homoaconitase (HACN) in the lysine biosynthesis pathway via alpha-aminoadipic acid. PhIPMI is thus considered a key to understanding the fundamental metabolism of the earliest organisms. We describe for the first time the crystal structure of PhIPMI-s, which displays dual substrate specificity. The crystal structure unexpectedly shows that four molecules create an interlocked assembly with intermolecular disulfide linkages having a skewed 222 point-group symmetry. Although the overall fold of the PhIPMI-s monomer is related closely to domain 4 of the aconitase (ACN), one alpha-helix in the ACN structure is replaced by a short loop with relatively high temperature factor values. Because this region is essential for discriminating the structurally similar substrate based on interactions with its diversified gamma-moiety, the loop structure in the PhIPMI-s must be dependent on the presence of a substrate. The flexibility of the loop region might be a structural basis for recognizing both hydrophobic and hydrophilic gamma-moieties of two distinct substrates, isopropylmalate and homocitrate.

PubMed: 15522288
DOI: 10.1016/j.jmb.2004.09.035

Experimental method

X-RAY DIFFRACTION (1.98 Å)