4u18
Crystal structure of human peroxisomal delta3,delta2, enoyl-CoA isomerase (ISO-ECI2)
Structural highlights
FunctionECI2_HUMAN Able to isomerize both 3-cis and 3-trans double bonds into the 2-trans form in a range of enoyl-CoA species. Has a preference for 3-trans substrates (By similarity). Publication Abstract from PubMedThe catalytic domain of the trimeric human Delta3 ,Delta2 -enoyl-CoA isomerase, type-2 (HsECI2) has the typical crotonase fold. In the active site of this fold two main chain NH groups form an oxyanion hole for binding the thioester oxygen of the 3E- or 3Z-enoyl-CoA substrate molecules. A catalytic glutamate is essential for the proton transfer between the substrate C2 and C4 atoms for forming the product, 2E-enoyl-CoA, which is a key intermediate in the beta-oxidation pathway. The active site is covered by the C-terminal helix-10. In HsECI2, the isomerase domain is extended at its N-terminus by an acyl-CoA binding protein (ACBP) domain. Small angle X-ray scattering of HsECI2 shows that the ACBP-domain protrudes out of the central isomerase trimer. X-ray crystallography of the isomerase domain trimer identifies the active site geometry. A tunnel, shaped by loop-2 and extending from the catalytic site to bulk solvent, suggests a likely mode of binding of the fatty acyl chains. Calorimetry data show that the separately expressed ACBP and isomerase domains bind tightly to fatty acyl-CoA molecules. The truncated isomerase variant (without ACBP domain) has significant enoyl-CoA isomerase activity; however, the full-length isomerase is more efficient. Structural enzymological studies of helix-10 variants show the importance of this helix for efficient catalysis. Its hydrophobic side chains, together with residues from loop-2 and loop-4, complete a hydrophobic cluster that covers the active site, thereby fixing the thioester moiety in a mode of binding competent for efficient catalysis. This article is protected by copyright. All rights reserved. Human Delta , Delta -enoyl-CoA isomerase, type-2: a structural enzymology study on the catalytic role of its ACBP-domain and helix-10.,Onwukwe GU, Kursula P, Koski MK, Schmitz W, Wierenga RK FEBS J. 2014 Dec 16. doi: 10.1111/febs.13179. PMID:25515061[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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