Crystal structure and molecular mechanism of an E/F type bilin lyase-isomerase

Kumarapperuma, Indika; Joseph, Kes Lynn; Biju, Linta M.; Tom, Irin P.; Weaver, Kourtney; Grébert, Théophile; Partensky, Frédéric; Schluchter, Wendy M.; Yang, Xiaojing

doi:10.1016/j.str.2022.01.007

Cited by 6 publications

(8 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Combined with the structural and mechanistic analyses previously performed on MpeQ ( Kumarapperuma et al, 2022 ), the present study demonstrated that there are residues within the substrate that influence the isomerization reaction of lyase/isomerases, a novel finding. A complete understanding of the mechanisms of these isomerase-capable lyases within the E/F clan is a main challenge for future studies.…”

Section: Discussionsupporting

confidence: 66%

“…Among the three clans of lyases, only some members of the E/F clan have been reported to have the capability to isomerize bilins during attachment ( Everroad et al, 2006 ; Shukla et al, 2012 ; Humily et al, 2013 ; Sanfilippo et al, 2016 ); moreover very few studies regarding the mechanism among substrate-bilin-enzyme interactions during the isomerization reaction have been explored ( Zhao et al, 2017 ; Kumarapperuma et al, 2022 ). The ability of a member of the E/F-type lyase family (in the present case MpeV) to behave as both a lyase and an isomerase to two very similar substrates has never been reported before and suggests the CpeB (and likely MpeB) substrate environment plays a role in the isomerization process.…”

Section: Discussionmentioning

confidence: 99%

“…One explanation for this phenomenon is steric hinderance of H141 within the binding pocket of WHCpeB due to its bulky side chain and its proximity to C50 on WHCpeB, the site of PEB A-ring attachment and subsequent location of the bond isomerization ( Figure 5 ). Alternatively, H141 may be involved in protonation/deprotonation or hydrogen-bonding dependent activity affecting the bilin conformation within the binding pocket ( Kumarapperuma et al, 2022 ). Our modeling suggested that H141 in CpeB is close to the ring B propionate of PEB.…”

Section: Discussionmentioning

confidence: 99%

“…Historically, E/F-type lyases including MpeV exhibit broad variation in chromophore and PBP substrate specificity, while demonstrating high binding-site specificity (e.g., which C residue). Kumarapperuma and collaborators recently determined the crystal structure of the lyase-isomerase MpeQ, proposed a mechanism for the reaction, and compared it to the mechanism for the related PEB lyase MpeW ( Kumarapperuma et al, 2022 ). For MpeQ, Tyrosine 318 was proposed to activate PEB, polarizing the C3 = C3 1 double bond.…”

Section: Discussionmentioning

confidence: 99%

“…The E/F lyases adopt all helical structures. While the crystal structure of the heterodimeric CpcE/F lyase was reported to adopt an α-helical structure of a solenoid shape ( Zhao et al, 2017 ), the recent crystal structure of a novel lyase-isomerase, MpeQ ( Kumarapperuma et al, 2022 ), suggested that a question mark-like architecture represents a common protein framework for both single chain and heterodimeric E/F lyases ( Andrade et al, 2001 ; Marcotrigiano et al, 2001 ; Kozo et al, 2002 ; Takano and Gusella, 2002 ; Scheer and Zhao, 2008 ; Schluchter et al, 2010 ; Zhao et al, 2017 ; Kumarapperuma et al, 2022 ). The S/U lyases exhibit a broad variation in chromophore and PBP substrate specificity but are highly specific with regard to C binding sites ( Shen et al, 2006 ; Saunée et al, 2008 ; Scheer and Zhao, 2008 ; Biswas et al, 2010 ; Schluchter et al, 2010 ; Kronfel et al, 2013 ; Zhou et al, 2014 ; Gasper et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

The phycoerythrobilin isomerization activity of MpeV in Synechococcus sp. WH8020 is prevented by the presence of a histidine at position 141 within its phycoerythrin-I β-subunit substrate

et al. 2022

Self Cite

View full text Add to dashboard Cite

Marine Synechococcus efficiently harvest available light for photosynthesis using complex antenna systems, called phycobilisomes, composed of an allophycocyanin core surrounded by rods, which in the open ocean are always constituted of phycocyanin and two phycoerythrin (PE) types: PEI and PEII. These cyanobacteria display a wide pigment diversity primarily resulting from differences in the ratio of the two chromophores bound to PEs, the green-light absorbing phycoerythrobilin and the blue-light absorbing phycourobilin. Prior to phycobiliprotein assembly, bilin lyases post-translationally catalyze the ligation of phycoerythrobilin to conserved cysteine residues on α- or β-subunits, whereas the closely related lyase-isomerases isomerize phycoerythrobilin to phycourobilin during the attachment reaction. MpeV was recently shown in Synechococcus sp. RS9916 to be a lyase-isomerase which doubly links phycourobilin to two cysteine residues (C50 and C61; hereafter C50, 61) on the β-subunit of both PEI and PEII. Here we show that Synechococcus sp. WH8020, which belongs to the same pigment type as RS9916, contains MpeV that demonstrates lyase-isomerase activity on the PEII β-subunit but only lyase activity on the PEI β-subunit. We also demonstrate that occurrence of a histidine at position 141 of the PEI β-subunit from WH8020, instead of a leucine in its counterpart from RS9916, prevents the isomerization activity by WH8020 MpeV, showing for the first time that both the substrate and the enzyme play a role in the isomerization reaction. We propose a structural-based mechanism for the role of H141 in blocking isomerization. More generally, the knowledge of the amino acid present at position 141 of the β-subunits may be used to predict which phycobilin is bound at C50, 61 of both PEI and PEII from marine Synechococcus strains.

show abstract

Section: Discussionsupporting

confidence: 66%