PDBsum entry 5d6j

Ligase/protein binding

PDB id: 5d6j

Contents

Protein chains

630 a.a.

74 a.a.

Ligands

ATP

Metals

_MG

Waters ×482

PDB id:

5d6j

Name:

Ligase/protein binding

Title:

Crystal structure of a mycobacterial protein

Structure:

Acyl-coa synthase. Chain: a. Synonym: fatty-acid-coa ligase fadd32. Engineered: yes. Ubiquitin-like protein smt3. Chain: b. Fragment: unp residues 21-94. Engineered: yes

Source:

Mycobacterium smegmatis (strain atcc 700084 / mc(2)155). Organism_taxid: 246196. Strain: atcc 700084 / mc(2)155. Gene: fadd32, msmeg_6393, msmei_6225. Expressed in: escherichia coli. Expression_system_taxid: 562. Saccharomyces cerevisiae (strain atcc 204508 / s288c).

Resolution:

2.25Å R-factor: 0.170 R-free: 0.206

Authors:

W.J.Li,L.J.Bi

Key ref:

W.Li et al. (2015). Crystal structure of FadD32, an enzyme essential for mycolic acid biosynthesis in mycobacteria. Sci Rep, 5, 15493. PubMed id: 26628098 DOI: 10.1038/srep15493

Date:

12-Aug-15 Release date: 02-Mar-16

Protein chain

A0R618  (A0R618_MYCS2) -  Long-chain-fatty-acid--AMP ligase FadD32 from Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155)

Seq: 630 a.a.

Struc: 630 a.a.

Protein chain

Q12306  (SMT3_YEAST) -  Ubiquitin-like protein SMT3 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 101 a.a.

Struc: 74 a.a.

Enzyme reactions

• Enzyme class: Chain A: E.C.6.2.1.20 - long-chain-fatty-acid--[acyl-carrier-protein] ligase.
• Reaction: a long-chain fatty acid + holo-[ACP] + ATP = a long-chain fatty acyl- [ACP] + AMP + diphosphate

long-chain fatty acid + holo-[ACP] (Bound ligand (Het Group name = ATP) corresponds exactly) + ATP = long-chain fatty acyl- [ACP] + AMP + diphosphate

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1038/srep15493

Sci Rep 5:15493 (2015)

PubMed id: 26628098

Crystal structure of FadD32, an enzyme essential for mycolic acid biosynthesis in mycobacteria.

W.Li, S.Gu, J.Fleming, L.Bi.

ABSTRACT

Fatty acid degradation protein D32 (FadD32), an enzyme required for mycolic acid biosynthesis and essential for mycobacterial growth, has recently been identified as a valid and promising target for anti-tuberculosis drug development. Here we report the crystal structures of Mycobacterium smegmatis FadD32 in the apo and ATP-bound states at 2.4 Å and 2.25 Å resolution, respectively. FadD32 consists of two globular domains connected by a flexible linker. ATP binds in a cleft at the interface between the N- and C-terminal domains and its binding induces significant local conformational changes in FadD32. The binding sites of meromycolic acid and phosphopantetheine are identified by structural comparison with other members of the adenylating enzyme superfamily. These results will improve our understanding of the catalytic mechanism of FadD32 and help in the design of inhibitors of this essential enzyme.