3LTW
The structure of mycobacterium marinum arylamine n-acetyltransferase in complex with hydralazine
Summary for 3LTW
| Entry DOI | 10.2210/pdb3ltw/pdb |
| Related | 2VFB 2VFC |
| Descriptor | Arylamine N-acetyltransferase Nat, 1-hydrazinophthalazine, FORMIC ACID, ... (4 entities in total) |
| Functional Keywords | mycobacterium marinum, aryalmine n-acetyl transferase, mmnat, hydralazine, mycobacterium tuberculosis, transferase |
| Biological source | Mycobacterium marinum |
| Total number of polymer chains | 1 |
| Total formula weight | 31127.18 |
| Authors | Abuhammad, A.M.,Lowe, E.D.,Fullam, E.,Noble, M.,Garman, E.F.,Sim, E. (deposition date: 2010-02-16, release date: 2010-07-07, Last modification date: 2024-03-20) |
| Primary citation | Abuhammad, A.M.,Lowe, E.D.,Fullam, E.,Noble, M.,Garman, E.F.,Sim, E. Probing the architecture of the Mycobacterium marinum arylamine N-acetyltransferase active site Protein Cell, 1:384-392, 2010 Cited by PubMed Abstract: Treatment of latent tuberculosis infection remains an important goal of global TB eradication. To this end, targets that are essential for intracellular survival of Mycobacterium tuberculosis are particularly attractive. Arylamine N-acetyltransferase (NAT) represents such a target as it is, along with the enzymes encoded by the associated gene cluster, essential for mycobacterial survival inside macrophages and involved in cholesterol degradation. Cholesterol is likely to be the fuel for M. tuberculosis inside macrophages. Deleting the nat gene and inhibiting the NAT enzyme prevents survival of the microorganism in macrophages and induces cell wall alterations, rendering the mycobacterium sensitive to antibiotics to which it is normally resistant. To date, NAT from M. marinum (MMNAT) is considered the best available model for NAT from M. tuberculosis (TBNAT). The enzyme catalyses the acetylation and propionylation of arylamines and hydrazines. Hydralazine is a good acetyl and propionyl acceptor for both MMNAT and TBNAT. The MMNAT structure has been solved to 2.1 Å resolution following crystallisation in the presence of hydralazine and is compared to available NAT structures. From the mode of ligand binding, features of the binding pocket can be identified, which point to a novel mechanism for the acetylation reaction that results in a 3-methyltriazolo[3,4-a]phthalazine ring compound as product. PubMed: 21203950DOI: 10.1007/s13238-010-0037-7 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.1 Å) |
Structure validation
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