9LR6

Zn-Carbonic Anhydrase II complexed with 3NPA at RT

Summary for 9LR6

• Entry DOI: 10.2210/pdb9lr6/pdb
• Related: 7Y2A
• Descriptor: Carbonic anhydrase 2, ZINC ION, 2-(3-NITROPHENYL)ACETIC ACID, ... (4 entities in total)
• Functional Keywords: carbonic anhydrase, enzyme mechanism, metalloenzymes, metal binding protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 29535.62

Authors

Kim, C.U.,Kim, J.K. (deposition date: 2025-01-29, release date: 2025-04-30, Last modification date: 2025-05-21)

Primary citation

Kim, J.K.,Lim, S.W.,Jeong, H.,Lee, C.,Kim, S.,Son, D.W.,Kumar, R.,Andring, J.T.,Lomelino, C.,Wierman, J.L.,Cohen, A.E.,Shin, T.J.,Ghim, C.M.,McKenna, R.,Jo, B.H.,Min, D.,Choi, J.M.,Kim, C.U.
Fast product release requires active-site water dynamics in carbonic anhydrase.
Nat Commun, 16:4404-4404, 2025

PubMed Abstract: Water plays an essential role in enzyme structure, stability, and the substantial rate enhancement of enzyme catalysis. However, direct observations linking enzyme catalysis and active-site water dynamics pose a significant challenge due to experimental difficulties. By integrating an ultraviolet (UV) photolysis technique with temperature-controlled X-ray crystallography, we track the catalytic pathway of carbonic anhydrase II (CAII) at 1.2 Å resolution. This approach enables us to construct molecular movies of CAII catalysis, encompassing substrate (CO) binding, conversion from substrate to product (bicarbonate), and product release. In the catalytic pathway, we identify an unexpected configuration in product binding and correlate it with sub-nanosecond rearrangement of active-site water. Based on these experimental observations, we propose a comprehensive mechanism of CAII and describe the detailed structure and dynamics of active-site water in CAII. Our findings suggest that CAII has evolved to utilize the structure and fast dynamics of the active-site waters for its diffusion-limited catalytic efficiency.

PubMed: 40355440
DOI: 10.1038/s41467-025-59645-x

Experimental method

X-RAY DIFFRACTION (1.25 Å)