PDBsum entry 2iwz

Transferase

PDB id: 2iwz

Contents

Protein chain

426 a.a. *

Ligands

6NA ×2

NH4 ×2

Waters ×686

* Residue conservation analysis

PDB id:

2iwz

Name:

Transferase

Title:

Human mitochondrial beta-ketoacyl acp synthase complexed with hexanoic acid

Structure:

3-oxoacyl-[acyl-carrier-protein] synthase. Chain: a, b. Fragment: residues 38-459. Synonym: beta-ketoacyl synthase. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli m15. Expression_system_taxid: 1007065. Expression_system_variant: prep4. Other_details: sumio sugano, university of tokyo supplied DNA

Resolution:

1.65Å R-factor: 0.156 R-free: 0.188

Authors:

C.E.Christensen,B.B.Kragelund,P.Von Wettstein-Knowles,A.Henriksen

Key ref:

C.E.Christensen et al. (2007). Structure of the human beta-ketoacyl [ACP] synthase from the mitochondrial type II fatty acid synthase. Protein Sci, 16, 261-272. PubMed id: 17242430 DOI: 10.1110/ps.062473707

Date:

05-Jul-06 Release date: 06-Feb-07

Protein chains

Q9NWU1  (OXSM_HUMAN) -  3-oxoacyl-[acyl-carrier-protein] synthase, mitochondrial from Homo sapiens

Seq: 459 a.a.

Struc: 426 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.2.3.1.41 - beta-ketoacyl-[acyl-carrier-protein] synthase I.
• Reaction: a fatty acyl-[ACP] + malonyl-[ACP] + H⁺ = a 3-oxoacyl-[ACP] + holo- [ACP] + CO2

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

Key reference

DOI no: 10.1110/ps.062473707

Protein Sci 16:261-272 (2007)

PubMed id: 17242430

Structure of the human beta-ketoacyl [ACP] synthase from the mitochondrial type II fatty acid synthase.

C.E.Christensen, B.B.Kragelund, P.von Wettstein-Knowles, A.Henriksen.

ABSTRACT

Two distinct ways of organizing fatty acid biosynthesis exist: the multifunctional type I fatty acid synthase (FAS) of mammals, fungi, and lower eukaryotes with activities residing on one or two polypeptides; and the dissociated type II FAS of prokaryotes, plastids, and mitochondria with individual activities encoded by discrete genes. The beta-ketoacyl [ACP] synthase (KAS) moiety of the mitochondrial FAS (mtKAS) is targeted by the antibiotic cerulenin and possibly by the other antibiotics inhibiting prokaryotic KASes: thiolactomycin, platensimycin, and the alpha-methylene butyrolactone, C75. The high degree of structural similarity between mitochondrial and prokaryotic KASes complicates development of novel antibiotics targeting prokaryotic KAS without affecting KAS domains of cytoplasmic FAS. KASes catalyze the C(2) fatty acid elongation reaction using either a Cys-His-His or Cys-His-Asn catalytic triad. Three KASes with different substrate specificities participate in synthesis of the C(16) and C(18) products of prokaryotic FAS. By comparison, mtKAS carries out all elongation reactions in the mitochondria. We present the X-ray crystal structures of the Cys-His-His-containing human mtKAS and its hexanoyl complex plus the hexanoyl complex of the plant mtKAS from Arabidopsis thaliana. The structures explain (1) the bimodal (C(6) and C(10)-C(12)) substrate preferences leading to the C(8) lipoic acid precursor and long chains for the membranes, respectively, and (2) the low cerulenin sensitivity of the human enzyme; and (3) reveal two different potential acyl-binding-pocket extensions. Rearrangements taking place in the active site, including subtle changes in the water network, indicate a change in cooperativity of the active-site histidines upon primer binding.

Selected figure(s)

Figure 2.
Figure 2. Ca RMSDs between (A) HsmtKAS and HsmtKAS:C6 and (B) AtmtKAS and AtmtKAS:C6. The tube diameter is

Figure 4.
Figure 4. Stereoviews of the HsmtKAS active site. (A) C6 in the acyl-binding pocket. Balls and sticks are colored according to atom

The above figures are reprinted from an Open Access publication published by the Protein Society: Protein Sci (2007, 16, 261-272) copyright 2007.

Figures were selected by an automated process.