5CA2: CONFORMATIONAL MOBILITY OF HIS-64 IN THE THR-200 (RIGHT ARROW) SER MUTANT OF HUMAN CARBONIC ANHYDRASE II

Citation:
Abstract
The three-dimensional structure of the Thr-200----Ser (T200S) mutant of human carbonic anhydrase II (CAII) has been determined by X-ray crystallographic methods at 2.1-A resolution. This particular mutant of CAII exhibits CO2 hydrase activity that is comparable to that of the wild-type enzyme with a 2-fold stabilization of the E.HCO3- complex and esterase activity that is 4-fold greater than that of the wild-type enzyme. The structure of the mutant enzyme reveals no significant local changes accompanying the conservative T200S substitution, but an important nonlocal structural change is evident: the side chain of catalytic residue His-64 rotates away from the active site by 105 degrees about chi 1 and apparently displaces a water molecule. The displaced water molecule is present in the wild-type enzyme; however, the electron density into which this water is built is interpretable as an alternate conformation of His-64 with 10-20% occupancy. The rate constants for proton transfer from the zinc-water ligand to His-64 and from His-64 to bulk solvent are maintained in the T200S variant; therefore, if His-64 is conformationally mobile about chi 1 and/or chi 2 during catalysis, compensatory changes in solvent configuration must sustain efficient proton transfer.
PDB ID: 5CA2Download
MMDB ID: 58477
PDB Deposition Date: 1991/6/8
Updated in MMDB: 2017/12
Experimental Method:
x-ray diffraction
Resolution: 2.1  Å
Source Organism:
Similar Structures:
Biological Unit for 5CA2: monomeric; determined by author
Molecular Components in 5CA2
Label Count Molecule
Protein (1 molecule)
1
Carbonic Anhydrase II(Gene symbol: CA2)
Molecule annotation
Chemicals (2 molecules)
1
1
2
1
* Click molecule labels to explore molecular sequence information.

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