8FG7
Apo mouse acidic mammalian chitinase, catalytic domain at 277 K
Summary for 8FG7
| Entry DOI | 10.2210/pdb8fg7/pdb |
| Related | 8FG5 |
| Descriptor | Acidic mammalian chitinase, MAGNESIUM ION (3 entities in total) |
| Functional Keywords | gh18 chitinase, acidic mammalian chitinase, hydrolase |
| Biological source | Mus musculus (house mouse) |
| Total number of polymer chains | 1 |
| Total formula weight | 44646.30 |
| Authors | Diaz, R.E.,Asthana, P.,Fraser, J.S. (deposition date: 2022-12-12, release date: 2023-03-01, Last modification date: 2024-10-09) |
| Primary citation | Diaz, R.E.,Ecker, A.K.,Correy, G.J.,Asthana, P.,Young, I.D.,Faust, B.,Thompson, M.C.,Seiple, I.B.,Van Dyken, S.J.,Locksley, R.M.,Fraser, J.S. Structural characterization of ligand binding and pH-specific enzymatic activity of mouse Acidic Mammalian Chitinase. Biorxiv, 2024 Cited by PubMed Abstract: Chitin is an abundant biopolymer and pathogen-associated molecular pattern that stimulates a host innate immune response. Mammals express chitin-binding and chitin-degrading proteins to remove chitin from the body. One of these proteins, Acidic Mammalian Chitinase (AMCase), is an enzyme known for its ability to function under acidic conditions in the stomach but is also active in tissues with more neutral pHs, such as the lung. Here, we used a combination of biochemical, structural, and computational modeling approaches to examine how the mouse homolog (mAMCase) can act in both acidic and neutral environments. We measured kinetic properties of mAMCase activity across a broad pH range, quantifying its unusual dual activity optima at pH 2 and 7. We also solved high resolution crystal structures of mAMCase in complex with oligomeric GlcNAcn, the building block of chitin, where we identified extensive conformational ligand heterogeneity. Leveraging these data, we conducted molecular dynamics simulations that suggest how a key catalytic residue could be protonated via distinct mechanisms in each of the two environmental pH ranges. These results integrate structural, biochemical, and computational approaches to deliver a more complete understanding of the catalytic mechanism governing mAMCase activity at different pH. Engineering proteins with tunable pH optima may provide new opportunities to develop improved enzyme variants, including AMCase, for therapeutic purposes in chitin degradation. PubMed: 37398339DOI: 10.1101/2023.06.03.542675 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.64 Å) |
Structure validation
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