PMID- 35647924
OWN - NLM
STAT- MEDLINE
DCOM- 20220603
LR  - 20220603
IS  - 2059-7983 (Electronic)
IS  - 2059-7983 (Linking)
VI  - 78
IP  - Pt 6
DP  - 2022 Jun 1
TI  - Structural visualization of transient interactions between the cis-acting 
      acyltransferase and acyl carrier protein of the salinomycin modular polyketide 
      synthase.
PG  - 779-791
LID - 10.1107/S2059798322004612 [doi]
AB  - Transient protein-protein interactions between cis-acting acyltransferase (AT) 
      and acyl carrier protein (ACP) domains are critical for the catalysis and 
      processivity of modular polyketide synthases (mPKSs), but are challenging for 
      structural characterization due to the intrinsically weak binding affinity. Here, 
      a stable complex of cis-acting AT and ACP domains from the ninth module of the 
      salinomycin mPKS was obtained using a maleimide cross-linker and the structure of 
      the complex was determined at 2.6 A resolution. The crystal structure shows that 
      the AT in combination with the ketosynthase (KS)-to-AT linker forms a C-shaped 
      architecture to embrace the ACP. The large hydrolase subdomain of the AT serves 
      as a major binding platform for the ACP, while the small ferredoxin-like 
      subdomain of the AT and the KS-to-AT linker cooperate with each other to 
      constrain binding of the ACP. The importance of interface residues in cis-acting 
      AT-ACP interactions was confirmed by mutagenesis assays. The interaction mode 
      observed in the cis-acting AT-ACP complex is completely different from those 
      observed in trans-acting AT-ACP complexes, where the ACP primarily contacts the 
      small domain of the AT. The complex structure provides detailed mechanistic 
      insights into AT-ACP recognition in cis-AT mPKSs.
FAU - Feng, Y
AU  - Feng Y
AUID- ORCID: 0000-0001-9709-8849
AD  - State Key Laboratory of Microbial Metabolism, School of Life Sciences and 
      Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Road, Minhang 
      District, Shanghai 200240, People's Republic of China.
FAU - Zhang, F
AU  - Zhang F
AD  - State Key Laboratory of Microbial Metabolism, School of Life Sciences and 
      Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Road, Minhang 
      District, Shanghai 200240, People's Republic of China.
FAU - Huang, S
AU  - Huang S
AD  - State Key Laboratory of Microbial Metabolism, School of Life Sciences and 
      Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Road, Minhang 
      District, Shanghai 200240, People's Republic of China.
FAU - Deng, Z
AU  - Deng Z
AD  - State Key Laboratory of Microbial Metabolism, School of Life Sciences and 
      Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Road, Minhang 
      District, Shanghai 200240, People's Republic of China.
FAU - Bai, L
AU  - Bai L
AD  - State Key Laboratory of Microbial Metabolism, School of Life Sciences and 
      Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Road, Minhang 
      District, Shanghai 200240, People's Republic of China.
FAU - Zheng, J
AU  - Zheng J
AD  - State Key Laboratory of Microbial Metabolism, School of Life Sciences and 
      Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Road, Minhang 
      District, Shanghai 200240, People's Republic of China.
LA  - eng
GR  - 2020YFA0907900/National Key R&D Program/
GR  - 32070040/National Natural Science Foundation of China/
PT  - Journal Article
DEP - 20220525
PL  - United States
TA  - Acta Crystallogr D Struct Biol
JT  - Acta crystallographica. Section D, Structural biology
JID - 101676043
RN  - 0 (Acyl Carrier Protein)
RN  - 0 (Pyrans)
RN  - 62UXS86T64 (salinomycin)
RN  - 79956-01-7 (Polyketide Synthases)
RN  - EC 2.3.- (Acyltransferases)
SB  - IM
MH  - *Acyl Carrier Protein/chemistry/metabolism
MH  - Acyltransferases/chemistry
MH  - *Polyketide Synthases/chemistry/metabolism
MH  - Pyrans
OTO - NOTNLM
OT  - acyl carrier proteins
OT  - acyltransferases
OT  - cross-linking
OT  - polyketides
OT  - protein-protein interactions
OT  - salinomycin modular polyketide synthases
EDAT- 2022/06/02 06:00
MHDA- 2022/06/07 06:00
CRDT- 2022/06/01 12:05
PHST- 2021/11/23 00:00 [received]
PHST- 2022/05/02 00:00 [accepted]
PHST- 2022/06/01 12:05 [entrez]
PHST- 2022/06/02 06:00 [pubmed]
PHST- 2022/06/07 06:00 [medline]
AID - S2059798322004612 [pii]
AID - 10.1107/S2059798322004612 [doi]
PST - ppublish
SO  - Acta Crystallogr D Struct Biol. 2022 Jun 1;78(Pt 6):779-791. doi: 
      10.1107/S2059798322004612. Epub 2022 May 25.