PDBsum entry 1lg5

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Lyase PDB id
Protein chain
257 a.a. *
Waters ×167
* Residue conservation analysis

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Key reference
Title Organization of an efficient carbonic anhydrase: implications for the mechanism based on structure-Function studies of a t199p/c206s mutant.
Authors S.Huang, B.Sjöblom, A.E.Sauer-Eriksson, B.H.Jonsson.
Ref. Biochemistry, 2002, 41, 7628-7635. [DOI no: 10.1021/bi020053o]
PubMed id 12056894
Substitution of Pro for Thr199 in the active site of human carbonic anhydrase II (HCA II)(1) reduces its catalytic efficiency about 3000-fold. X-ray crystallographic structures of the T199P/C206S variant have been determined in complex with the substrate bicarbonate and with the inhibitors thiocyanate and beta-mercaptoethanol. The latter molecule is normally not an inhibitor of wild-type HCA II. All three ligands display novel binding interactions to the T199P/C206S mutant. The beta-mercaptoethanol molecule binds in the active site area with its sulfur atom tetrahedrally coordinated to the zinc ion. Thiocyanate binds tetrahedrally coordinated to the zinc ion in T199P/C206S, in contrast to its pentacoordinated binding to the zinc ion in wild-type HCA II. Bicarbonate binds to the mutant with two of its oxygens at the positions of the zinc water (Wat263) and Wat318 in wild-type HCA II. The environment of this area is more hydrophilic than the normal bicarbonate-binding site of HCA II situated in the hydrophobic part of the cavity normally occupied by the so-called deep water (Wat338). The observation of a new binding site for bicarbonate has implications for understanding the mechanism by which the main-chain amino group of Thr199 acquired an important role for orientation of the substrate during the evolution of the enzyme.
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