TY - JOUR
T1 - A locking mechanism preventing radical damage in the absence of substrate, as revealed by the x-ray structure of lysine 5,6-aminomutase
AU - Berkovitch, Frederick
AU - Behshad, Elham
AU - Tang, Kuo Hsiang
AU - Enns, Eva A.
AU - Frey, Perry A.
AU - Drennan, Catherine L.
PY - 2004/11/9
Y1 - 2004/11/9
N2 - Lysins 5,6-aminomutase is an adenosylcobalamin and pyridoxal-5′- phosphate-dependent enzyme that catalyzes a 1,2 rearrangement of the terminal amino group of DL-lysine and of L-β-lysine. We have solved the x-ray structure of a substrate-free form of lysine-5,6-aminomutase from Clostridium sticklandii. In this structure, a Rossmann domain covalently binds pyridoxal-5′-phosphate by means of lysine 144 and positions it into the putative active site of a neighboring triosephosphate isomerase barrel domain, while simultaneously positioning the other cofactor, adenosylcobalamin, ≈25 Å from the active site. In this mode of pyridoxal-5′-phosphate binding, the cofactor acts as an anchor, tethering the separate polypeptide chain of the Rossmann domain to the triosephosphate isomerase barrel domain. Upon substrate binding and transaldimination of the lysine-144 linkage, the Rossmann domain would be free to rotate and bring adenosylcobalamin, pyridoxal-5′-phosphate, and substrate into proximity. Thus, the structure embodies a locking mechanism to keep the adenosylcobalamin out of the active site and prevent radical generation in the absence of substrate.
AB - Lysins 5,6-aminomutase is an adenosylcobalamin and pyridoxal-5′- phosphate-dependent enzyme that catalyzes a 1,2 rearrangement of the terminal amino group of DL-lysine and of L-β-lysine. We have solved the x-ray structure of a substrate-free form of lysine-5,6-aminomutase from Clostridium sticklandii. In this structure, a Rossmann domain covalently binds pyridoxal-5′-phosphate by means of lysine 144 and positions it into the putative active site of a neighboring triosephosphate isomerase barrel domain, while simultaneously positioning the other cofactor, adenosylcobalamin, ≈25 Å from the active site. In this mode of pyridoxal-5′-phosphate binding, the cofactor acts as an anchor, tethering the separate polypeptide chain of the Rossmann domain to the triosephosphate isomerase barrel domain. Upon substrate binding and transaldimination of the lysine-144 linkage, the Rossmann domain would be free to rotate and bring adenosylcobalamin, pyridoxal-5′-phosphate, and substrate into proximity. Thus, the structure embodies a locking mechanism to keep the adenosylcobalamin out of the active site and prevent radical generation in the absence of substrate.
UR - http://www.scopus.com/inward/record.url?scp=8644265127&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=8644265127&partnerID=8YFLogxK
U2 - 10.1073/pnas.0407074101
DO - 10.1073/pnas.0407074101
M3 - Article
C2 - 15514022
AN - SCOPUS:8644265127
SN - 0027-8424
VL - 101
SP - 15870
EP - 15875
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 45
ER -