1yo2
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Proton Transfer from His200 in Human Carbonic Anhydrase II
OverviewOverview
Human carbonic anhydrase II (HCA II) has a histidine at position 64, (His64) that donates a proton to the zinc-bound hydroxide in catalysis of, the dehydration of bicarbonate. To examine the effect of the histidine, location on proton shuttling, His64 was replaced with Ala and Thr200, replaced with histidine (H64A-T200H HCAII), effectively relocating the, proton shuttle residue 2 A closer to the zinc-bound hydroxide compared to, wild type HCA II. The crystal structure of H64A-T200H HCA II at 1.8 A, resolution shows the side chain of His200 directly hydrogen-bonded with, the zinc-bound solvent. Different proton transfer processes were observed, at pH 6 and at pH 8 during the catalytic hydration-dehydration cycle, measured by mass spectrometry as the depletion of 18O from C18O2 by, H64A-T200H HCA II. The process at pH 6.0 is attributed to proton transfer, between the side chain of His200 and the zinc-bound hydroxide, in analogy, with proton transfer involving His64 in wild-type HCA II. At pH 8.0 it is, attributed to proton transfer between bicarbonate and the zinc-bound, hydroxide, as supported by the dependence of the rate of proton transfer, on bicarbonate concentration and on solvent hydrogen isotope effects. This, study establishes that a histidine directly hydrogen-bonded to the, zinc-bound hydroxide, can adopt the correct distance geometry to support, proton transfer
DiseaseDisease
Known disease associated with this structure: Osteopetrosis, autosomal recessive 3, with renal tubular acidosis OMIM:[611492]
About this StructureAbout this Structure
1YO2 is a Single protein structure of sequence from Homo sapiens with ZN as ligand. Active as Carbonate dehydratase, with EC number 4.2.1.1 Full crystallographic information is available from OCA.
ReferenceReference
Proton transfer in a Thr200His mutant of human carbonic anhydrase II., Bhatt D, Tu C, Fisher SZ, Hernandez Prada JA, McKenna R, Silverman DN, Proteins. 2005 Nov 1;61(2):239-45. PMID:16106378
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