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PDBsum entry 1hed

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Lyase(oxo-acid) PDB id
1hed
Jmol
Contents
Protein chain
255 a.a.
Metals
_HG ×2
_ZN
Waters ×107

References listed in PDB file
Key reference
Title Structural consequences of hydrophilic amino acid substitutions in the hydrophobic pocket of human carbonic anhydrase ii.
Authors S.K.Nair, D.W.Christianson.
Ref. Biochemistry, 1993, 32, 4506-4514. [DOI no: 10.1021/bi00068a005]
PubMed id 8485129
Note In the PDB file this reference is annotated as "TO BE PUBLISHED". The citation details given above were identified by an automated search of PubMed on title and author names, giving a percentage match of 84%.
Abstract
The three-dimensional structures of Leu-198-->Glu, Leu-198-->His, Leu-198-->Arg, and Leu-198-->Ala variants of human carbonic anhydrase II (CAII) have each been determined by X-ray crystallographic methods to a resolution of 2.0 A. The side chain of Leu-198 is located at the mouth of the active site hydrophobic pocket, and this pocket is required for substrate association. Hydrophobic-->hydrophilic amino acid substitutions at the mouth of the pocket decrease kcat/KM for CO2 hydration: the CO2 hydrase activities of Leu-198-->Glu, Leu-198-->His, and Leu-198-->Arg CAIIs are diminished 19-fold, 10-fold, and 17-fold, respectively, relative to the wild-type enzyme; however, the substitution of a compact aliphatic side chain for Leu-198 has a smaller effect on catalysis, in that Leu-198-->Ala CAII exhibits only a 3-fold decrease in CO2 hydrase activity [Krebs, J. F., Rana, F., Dluhy, R. A., & Fierke, C. A. (1993) Biochemistry (preceding paper in this issue)]. It is intriguing that CO2 hydrase activity is not severely diminished in Leu-198-->Arg CAII, even though the side chain of Arg-198 blocks the hydrophobic pocket. Therefore, the bulky side chain of Arg-198 must be reasonably mobile in order to accommodate substrate association. Significantly, a residue larger than the wild-type Leu-198 side chain does not necessarily block the substrate association pocket; e.g., the side chain of Glu-198 packs against a hydrophobic patch, the net result of which is a wider mouth for the pocket.(ABSTRACT TRUNCATED AT 250 WORDS)
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