PXD043977

PXD043977 is an original dataset announced via ProteomeXchange.

Title	HadBD dehydratase from Mycobacterium tuberculosis FAS-II: a singular structure for a unique function
Description	Mycolic acids (MAs) are a unique class of lipids that are essential for viability, virulence and persistence of Mycobacterium tuberculosis (Mtb). Therefore, enzymes involved in MAs biosynthesis represent important class of drug targets. We previously showed that (3R)-hydroxyacyl-ACP dehydratase (HAD) protein HadD is dedicated mainly to the production of keto-MAs and plays a determinant role in Mtb virulence. Here, we discovered that HAD activity requires formation of a tight heterotetramer between HadD and HadB, a HAD unit coded by a distinct chromosomal region. Using biochemical, structural and cell-based analyses, we showed that HadB is the catalytic subunit, whereas HadD is involved in substrate binding. We identified determinants of the ultra-long-chain lipid substrate specificity and revealed details of structure-function relationship. Taken together, our study shows that HadBD, and not HadD, is the biologically relevant functional unit, and these results have important implications for designing innovative antivirulence molecules to fight tuberculosis.
HostingRepository	PRIDE
AnnounceDate	2024-03-21
AnnouncementXML	Submission_2024-03-21_03:08:12.266.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Manuelle Ducoux-Petit
SpeciesList	scientific name: Mycobacterium bovis BCG str. Pasteur 1173P2; NCBI TaxID: 410289;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-21 02:50:14	ID requested
⏵ 1	2024-03-21 03:08:12	announced

10.1002/PRO.4964;

submitter keyword: (3R)-hydroxyacyl-ACP dehydratase, structure-function relationships., mycolic acids, hydratase 2,Mycobacterium tuberculosis, hotdog fold, crystal structure, catalytic subunit, substrate specificity, fatty acid synthase type II system

Burlet-Schiltz Odile
contact affiliation	Institut de Pharmacologie et de Biologie Structurale (IPBS), Université de Toulouse, CNRS, Université Toulouse III - Paul Sabatier (UT3), Toulouse, 31077, France
contact email	Odile.Schiltz@ipbs.fr
lab head
Manuelle Ducoux-Petit
contact affiliation	CNRS
contact email	manuelle.ducoux@ipbs.fr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD043977
     1. Label: PRIDE project
     2. Name: HadBD dehydratase from Mycobacterium tuberculosis FAS-II: a singular structure for a unique function