Premium
R‐ to T‐ Transition in Fructose‐1,6‐bisphosphatase: Loop Displacement is the Penultimate Step to Inactivation
Author(s) -
Gao Yang,
Iancu Cristina V,
Mukund Susmith,
Honzatko Richard B
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.468.2
Subject(s) - steric effects , loop (graph theory) , protein subunit , chemistry , fructose 1,6 bisphosphatase , protein quaternary structure , side chain , stereochemistry , molecular dynamics , crystallography , fructose , biochemistry , computational chemistry , mathematics , organic chemistry , combinatorics , gene , polymer
AMP transforms fructose‐1, 6‐bisphosphatase (FBPase) from its active R‐state to its inactive T‐state. During this quaternary transition, a catalytically essential loop (residues 52–72) leaves the active site (engaged conformation) and moves to its inactive (disengaged) conformation. Structures of FBPase and molecular dynamic simulations reveal the mechanism of loop displacement. The AMP complex of Asp 10 FBPase provides the first example of an engaged dynamic loop in a near‐T quaternary state. Subunit rotation forces loop 190 (from subunit C1) into contact with the hinge (residues 52–57) of the dynamic loop of subunit C2. Additional conformational changes in residues 264–274 of subunit C2 reduce space available to the engaged conformation of loop 52–72. Target Molecular Dynamics indicates the absence of steric barriers in subunit rotations but requires the displacement of the loop 50–72 from its engaged conformation in order to achieve the T‐state. Principal Component Analysis reveals anti‐correlated motions, which cause steric clashes consistent with the displacement of loop 52–72 from its engaged conformation. This research is supported by NIH grant NS 10546.