Informace o publikaci

Atypical homodimerization revealed by the structure of the (S)-enantioselective haloalkane dehalogenase DmmarA from Mycobacterium marinum

Logo poskytovatele
Logo poskytovatele
Logo poskytovatele
Logo poskytovatele
Logo poskytovatele
Autoři

ŠNAJDAROVÁ Karolína MARQUES Sérgio Manuel DAMBORSKÝ Jiří BEDNÁŘ David MAREK Martin

Rok publikování 2023
Druh Článek v odborném periodiku
Časopis / Zdroj Acta Crystallographica Section D: Structural Biology
Fakulta / Pracoviště MU

Přírodovědecká fakulta

Citace
www https://journals.iucr.org/d/issues/2023/11/00/jc5060/index.html
Doi http://dx.doi.org/10.1107/S2059798323006642
Klíčová slova haloalkane dehalogenases; Mycobacterium marinum; DmmarA; homodimerization; surface loops; enantioselectivity; X-ray crystallography; SAXS
Přiložené soubory
Popis Haloalkane dehalogenases (HLDs) are a family of alpha/beta-hydrolase fold enzymes that employ S(N)2 nucleophilic substitution to cleave the carbon-halogen bond in diverse chemical structures, the biological role of which is still poorly understood. Atomic-level knowledge of both the inner organization and supramolecular complexation of HLDs is thus crucial to understand their catalytic and noncatalytic functions. Here, crystallographic structures of the (S)-enantioselective haloalkane dehalogenase DmmarA from the waterborne pathogenic microbe Mycobacterium marinum were determined at 1.6 and 1.85 angstrom resolution. The structures show a canonical alpha beta alpha-sandwich HLD fold with several unusual structural features. Mechanistically, the atypical composition of the proton-relay catalytic triad (aspartate-histidine-aspartate) and uncommon active-site pocket reveal the molecular specificities of a catalytic apparatus that exhibits a rare (S)-enantiopreference. Additionally, the structures reveal a previously unobserved mode of symmetric homodimerization, which is predominantly mediated through unusual L5-to-L5 loop interactions. This homodimeric association in solution is confirmed experimentally by data obtained from small-angle X-ray scattering. Utilizing the newly determined structures of DmmarA, molecular modelling techniques were employed to elucidate the underlying mechanism behind its uncommon enantioselectivity. The (S)-preference can be attributed to the presence of a distinct binding pocket and variance in the activation barrier for nucleophilic substitution.
Související projekty:

Používáte starou verzi internetového prohlížeče. Doporučujeme aktualizovat Váš prohlížeč na nejnovější verzi.

Další info