PDBsum entry 2fhs

Oxidoreductase/biosynthetic protein

PDB id

2fhs

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Contents

			Protein chains

					258 a.a. *


					57 a.a. *

			Waters ×79

* Residue conservation analysis

PDB id:

2fhs

Links
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Name:

Oxidoreductase/biosynthetic protein

Title:

Structure of acyl carrier protein bound to fabi, the enoyl reductase from escherichia coli

Structure:

Enoyl-[acyl-carrier-protein] reductase, nadh-dependent. Chain: a, b. Engineered: yes. Acyl carrier protein. Chain: c. Synonym: acp, cytosolic-activating factor, caf, fatty acid synthase acyl carrier protein. Engineered: yes

Source:

Escherichia coli. Organism_taxid: 316407. Strain: str. K12 substr. W3110. Expressed in: escherichia coli. Expression_system_taxid: 562. Organism_taxid: 562. Gene: acpp. Expression_system_taxid: 562

Biol. unit:

Monomer (from PDB file)

Resolution:

2.70Å

R-factor:

0.226

R-free:

0.263

Authors:

S.Kolappan,P.Novichenok,S.Rafi,C.Simmerling,P.J.Tonge,C.Kisker

Key ref:

S.Rafi et al. (2006). Structure of acyl carrier protein bound to FabI, the FASII enoyl reductase from Escherichia coli. J Biol Chem, 281, 39285-39293. PubMed id: 17012233 DOI: 10.1074/jbc.M608758200

Date:

27-Dec-05

Release date:

17-Oct-06

PROCHECK

	Headers

	References

Protein chains

P0AEK4 (FABI_ECOLI) - Enoyl-[acyl-carrier-protein] reductase [NADH] FabI from Escherichia coli (strain K12)

Seq: Struc:					262 a.a. 258 a.a.

Protein chain

P0A6A8 (ACP_ECOLI) - Acyl carrier protein from Escherichia coli (strain K12)

Seq: Struc:					78 a.a. 57 a.a.

Key:

PfamA domain

Secondary structure

CATH domain



		Enzyme reactions

Enzyme class 2:

Chains A, B: E.C.1.3.1.9 - enoyl-[acyl-carrier-protein] reductase (NADH).

[IntEnz] [ExPASy] [KEGG] [BRENDA]

Reaction:

a 2,3-saturated acyl-[ACP] + NAD⁺ = a (2E)-enoyl-[ACP] + NADH + H⁺

2,3-saturated acyl-[ACP]	+	NAD(+)	=	(2E)-enoyl-[ACP]	+	NADH	+	H(+)

Enzyme class 3:

Chain C: E.C.?

[IntEnz] [ExPASy] [KEGG] [BRENDA]

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

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

Added reference

DOI no: 10.1074/jbc.M608758200	J Biol Chem 281:39285-39293 (2006)
PubMed id: 17012233

Structure of acyl carrier protein bound to FabI, the FASII enoyl reductase from Escherichia coli.
S.Rafi, P.Novichenok, S.Kolappan, X.Zhang, C.F.Stratton, R.Rawat, C.Kisker, C.Simmerling, P.J.Tonge.

ABSTRACT

Acyl carrier proteins play a central role in metabolism by transporting substrates in a wide variety of pathways including the biosynthesis of fatty acids and polyketides. However, despite their importance, there is a paucity of direct structural information concerning the interaction of ACPs with enzymes in these pathways. Here we report the structure of an acyl-ACP substrate bound to the Escherichia coli fatty acid biosynthesis enoyl reductase enzyme (FabI), based on a combination of x-ray crystallography and molecular dynamics simulation. The structural data are in agreement with kinetic studies on wild-type and mutant FabIs, and reveal that the complex is primarily stabilized by interactions between acidic residues in the ACP helix alpha2 and a patch of basic residues adjacent to the FabI substrate-binding loop. Unexpectedly, the acyl-pantetheine thioester carbonyl is not hydrogen-bonded to Tyr(156), a conserved component of the short chain alcohol dehydrogenase/reductase superfamily active site triad. FabI is a proven target for drug discovery and the present structure provides insight into the molecular determinants that regulate the interaction of ACPs with target proteins.

Selected figure(s)



	Figure 4. FIGURE 4. The structure of ACP bound to FabI following MD simulations. Final structure of the FabI·ACP complex. FabI is colored green and ACP is colored cyan. The figure was made with pymol (64).		Figure 5. FIGURE 5. Interactions between FabI and ACP. A, interactions between ACP (cyan) and FabI (green) at the helix 2 (ACP)-helix 8 (FabI) interface. B, interactions between crotonyl-pantetheine and FabI. The pantetheine (cyan) is hydrogen bonded to residues in FabI helix 8 (green). FabI residues in the conserved active site triad (Tyr^146, Tyr^156, and Lys^163) are colored yellow. The crotonyl group of the substrate (cyan) is bound in the s-trans conformation and the crotonyl carbonyl group is oriented toward Tyr^146 (yellow). The C-3 carbon of the crotonyl group is 3 Å from the NADH pro4(S) proton (white). In addition, the NADH ribose (cyan) is hydrogen bonded to Tyr^156 and Lys^163. The figure was made with pymol (64).

Figures were selected by an automated process.

Literature references that cite this PDB file's key reference

PubMed id

Reference

21393229

N.Liu, J.E.Cummings, K.England, R.A.Slayden, and P.J.Tonge (2011).
Mechanism and inhibition of the FabI enoyl-ACP reductase from Burkholderia pseudomallei.

J Antimicrob Chemother, 66, 564-573.

20662770

D.I.Chan, and H.J.Vogel (2010).
Current understanding of fatty acid biosynthesis and the acyl carrier protein.

Biochem J, 430, 1.

20055482

H.Lu, and P.J.Tonge (2010).
Mechanism and inhibition of the FabV enoyl-ACP reductase from Burkholderia mallei.

Biochemistry, 49, 1281-1289.

21127271

S.Kapur, A.Y.Chen, D.E.Cane, and C.Khosla (2010).
Molecular recognition between ketosynthase and acyl carrier protein domains of the 6-deoxyerythronolide B synthase.

Proc Natl Acad Sci U S A, 107, 22066-22071.

20731893

T.Maier, M.Leibundgut, D.Boehringer, and N.Ban (2010).
Structure and function of eukaryotic fatty acid synthases.

Q Rev Biophys, 43, 373-422.

18561189

J.G.McCoy, H.D.Johnson, S.Singh, C.A.Bingman, I.K.Lei, J.S.Thorson, and G.N.Phillips (2009).
Structural characterization of CalO2: a putative orsellinic acid P450 oxidase in the calicheamicin biosynthetic pathway.

Proteins, 74, 50-60.

PDB code:

3buj

19550039

M.J.Li, A.Q.Li, H.Xia, C.Z.Zhao, C.S.Li, S.B.Wan, Y.P.Bi, and X.J.Wang (2009).
Cloning and sequence analysis of putative type II fatty acid synthase genes from Arachis hypogaea L.

J Biosci, 34, 227-238.

19381365

P.Beltran-Alvarez, C.J.Arthur, R.J.Cox, J.Crosby, M.P.Crump, and T.J.Simpson (2009).
Preliminary kinetic analysis of acyl carrier protein-ketoacylsynthase interactions in the actinorhodin minimal polyketide synthase.

Mol Biosyst, 5, 511-518.

19151923

R.P.Massengo-Tiassé, and J.E.Cronan (2009).
Diversity in enoyl-acyl carrier protein reductases.

Cell Mol Life Sci, 66, 1507-1517.

18809688

D.I.Chan, T.Stockner, D.P.Tieleman, and H.J.Vogel (2008).
Molecular dynamics simulations of the Apo-, Holo-, and acyl-forms of Escherichia coli acyl carrier protein.

J Biol Chem, 283, 33620-33629.

18059524

D.M.Byers, and H.Gong (2007).
Acyl carrier protein: structure-function relationships in a conserved multifunctional protein family.

Biochem Cell Biol, 85, 649-662.

17420210

J.H.Yum, C.K.Kim, D.Yong, K.Lee, Y.Chong, C.M.Kim, J.M.Kim, S.Ro, and J.M.Cho (2007).
In vitro activities of CG400549, a novel FabI inhibitor, against recently isolated clinical staphylococcal strains in Korea.

Antimicrob Agents Chemother, 51, 2591-2593.

17327670

S.P.Muench, S.T.Prigge, R.McLeod, J.B.Rafferty, M.J.Kirisits, C.W.Roberts, E.J.Mui, and D.W.Rice (2007).
Studies of Toxoplasma gondii and Plasmodium falciparum enoyl acyl carrier protein reductase and implications for the development of antiparasitic agents.

Acta Crystallogr D Biol Crystallogr, 63, 328-338.

PDB codes:

2o2s 2o2y 2o50

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.