5DVX

Crystal structure of the catalytic-domain of human carbonic anhydrase IX at 1.6 angstrom resolution

Summary for 5DVX

• Entry DOI: 10.2210/pdb5dvx/pdb
• Descriptor: Carbonic anhydrase 9, ZINC ION, GLYCEROL, ... (6 entities in total)
• Functional Keywords: carbonic anhydrase ix, catalytic domain, water network, lyase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 58084.79

Authors

Mahon, B.P.,Socorro, L.,Driscoll, J.M.,McKenna, R. (deposition date: 2015-09-21, release date: 2016-08-03, Last modification date: 2024-10-30)

Primary citation

Mahon, B.P.,Bhatt, A.,Socorro, L.,Driscoll, J.M.,Okoh, C.,Lomelino, C.L.,Mboge, M.Y.,Kurian, J.J.,Tu, C.,Agbandje-McKenna, M.,Frost, S.C.,McKenna, R.
The Structure of Carbonic Anhydrase IX Is Adapted for Low-pH Catalysis.
Biochemistry, 55:4642-4653, 2016

PubMed Abstract: Human carbonic anhydrase IX (hCA IX) expression in many cancers is associated with hypoxic tumors and poor patient outcome. Inhibitors of hCA IX have been used as anticancer agents with some entering Phase I clinical trials. hCA IX is transmembrane protein whose catalytic domain faces the extracellular tumor milieu, which is typically associated with an acidic microenvironment. Here, we show that the catalytic domain of hCA IX (hCA IX-c) exhibits the necessary biochemical and biophysical properties that allow for low pH stability and activity. Furthermore, the unfolding process of hCA IX-c appears to be reversible, and its catalytic efficiency is thought to be correlated directly with its stability between pH 3.0 and 8.0 but not above pH 8.0. To rationalize this, we determined the X-ray crystal structure of hCA IX-c to 1.6 Å resolution. Insights from this study suggest an understanding of hCA IX-c stability and activity in low-pH tumor microenvironments and may be applicable to determining pH-related effects on enzymes.

PubMed: 27439028
DOI: 10.1021/acs.biochem.6b00243

Experimental method

X-RAY DIFFRACTION (1.598 Å)