6PDV

Cu-Carbonic Anhydrase II, A Nitrite Reductase

Summary for 6PDV

• Entry DOI: 10.2210/pdb6pdv/pdb
• Descriptor: Carbonic anhydrase 2, COPPER (II) ION, 2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL, ... (5 entities in total)
• Functional Keywords: nitrite reductase, metal substitution, lyase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 29584.30

Authors

Andring, J.T.,McKenna, R. (deposition date: 2019-06-19, release date: 2020-03-11, Last modification date: 2023-10-11)

Primary citation

Andring, J.T.,Kim, C.U.,McKenna, R.
Structure and mechanism of copper-carbonic anhydrase II: a nitrite reductase.
Iucrj, 7:287-293, 2020

PubMed Abstract: Nitric oxide (NO) promotes vasodilation through the activation of guanylate cyclase, resulting in the relaxation of the smooth muscle vasculature and a subsequent decrease in blood pressure. Therefore, its regulation is of interest for the treatment and prevention of heart disease. An example is pulmonary hypertension which is treated by targeting this NO/vasodilation pathway. In bacteria, plants and fungi, nitrite (NO ) is utilized as a source of NO through enzymes known as nitrite reductases. These enzymes reduce NO to NO through a catalytic metal ion, often copper. Recently, several studies have shown nitrite reductase activity of mammalian carbonic anhydrase II (CAII), yet the molecular basis for this activity is unknown. Here we report the crystal structure of copper-bound human CAII (Cu-CAII) in complex with NO at 1.2 Å resolution. The structure exhibits Type 1 (T-1) and 2 (T-2) copper centers, analogous to bacterial nitrite reductases, both required for catalysis. The copper-substituted CAII active site is penta-coordinated with a 'side-on' bound NO , resembling a T-2 center. At the N terminus, several residues that are normally disordered form a porphyrin ring-like configuration surrounding a second copper, acting as a T-1 center. A structural comparison with both apo- (without metal) and zinc-bound CAII (Zn-CAII) provides a mechanistic picture of how, in the presence of copper, CAII, with minimal conformational changes, can function as a nitrite reductase.

PubMed: 32148856
DOI: 10.1107/S2052252520000986

Experimental method

X-RAY DIFFRACTION (1.23 Å)