Myroilysin Is a New Bacterial Member of the M12A Family of Metzincin Metallopeptidases and Is Activated by a Cysteine Switch Mechanism

Xu, Dongqing; Zhou, Jiawu; Lou, Xiangdi; He, Jianhua; Ran, Tingting; Wang, Weiwu

doi:10.1074/jbc.m116.758110

Cited by 11 publications

(16 citation statements)

References 63 publications

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“…Target 2016‐07‐30_00000063_1 (Myroilysin, PDB ID 5CZW, Figure ) illustrates the details of the lDDT‐BS analyses. Myroilysin is a new bacterial member of the M12A family of metzincin metallopeptidases and activated by a cysteine‐switch mechanism.…”

Section: Resultsmentioning

confidence: 99%

Continuous Automated Model EvaluatiOn (CAMEO) complementing the critical assessment of structure prediction in CASP12

et al. 2017

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Every second year, the community experiment "Critical Assessment of Techniques for Structure Prediction" (CASP) is conducting an independent blind assessment of structure prediction methods, providing a framework for comparing the performance of different approaches and discussing the latest developments in the field. Yet, developers of automated computational modeling methods clearly benefit from more frequent evaluations based on larger sets of data. The "Continuous Automated Model EvaluatiOn (CAMEO)" platform complements the CASP experiment by conducting fully automated blind prediction assessments based on the weekly pre-release of sequences of those structures, which are going to be published in the next release of the PDB Protein Data Bank. CAMEO publishes weekly benchmarking results based on models collected during a 4-day prediction window, on average assessing ca. 100 targets during a time frame of 5 weeks. CAMEO benchmarking data is generated consistently for all participating methods at the same point in time, enabling developers to benchmark and cross-validate their method's performance, and directly refer to the benchmarking results in publications. In order to facilitate server development and promote shorter release cycles, CAMEO sends weekly email with submission statistics and low performance warnings. Many participants of CASP have successfully employed CAMEO when preparing their methods for upcoming community experiments. CAMEO offers a variety of scores to allow benchmarking diverse aspects of structure prediction methods. By introducing new scoring schemes, CAMEO facilitates new development in areas of active research, for example, modeling quaternary structure, complexes, or ligand binding sites.

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Section: Resultsmentioning

confidence: 99%

Continuous Automated Model EvaluatiOn (CAMEO) complementing the critical assessment of structure prediction in CASP12

et al. 2017

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“…To date, the crystal structures of crayfish pro-astacin (PDB entry 3lq0; Guevara et al, 2010), human pro-meprin (PDB entry 4gwm; Arolas et al, 2012) and pro-myroilysin from two closely related bacterial species, Myroides profundi (PDB entry 5czw; Xu et al, 2017) and Myroides sp. CSLB8 (PDB entry 5gwd; Xu et al, 2017), have been reported, as well as their respective mature forms astacin (PDB entry 1ast; Gomis-Ru ¨th et al, 1993), meprin (PDB entry 4gwn; Arolas et al, 2012) and myroilysin from Myroides sp. CSLB8 (PDB entry 5zjk; Ran et al, 2020).…”

Section: Comparison With Other Astacin Latency Mechanismsmentioning

confidence: 99%

Zymogenic latency in an ∼250-million-year-old astacin metallopeptidase

Guevara¹,

Rodríguez-Banqueri²,

Stöcker³

et al. 2022

Acta Cryst Sect D Struct Biol

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The horseshoe crab Limulus polyphemus is one of few extant Limulus species, which date back to ∼250 million years ago under the conservation of a common Bauplan documented by fossil records. It possesses the only proteolytic blood-coagulation and innate immunity system outside vertebrates and is a model organism for the study of the evolution and function of peptidases. The astacins are a family of metallopeptidases that share a central ∼200-residue catalytic domain (CD), which is found in >1000 species across holozoans and, sporadically, bacteria. Here, the zymogen of an astacin from L. polyphemus was crystallized and its structure was solved. A 34-residue, mostly unstructured pro-peptide (PP) traverses, and thus blocks, the active-site cleft of the CD in the opposite direction to a substrate. A central `PP motif' (F35-E-G-D-I39) adopts a loop structure which positions Asp38 to bind the catalytic metal, replacing the solvent molecule required for catalysis in the mature enzyme according to an `aspartate-switch' mechanism. Maturation cleavage of the PP liberates the cleft and causes the rearrangement of an `activation segment'. Moreover, the mature N-terminus is repositioned to penetrate the CD moiety and is anchored to a buried `family-specific' glutamate. Overall, this mechanism of latency is reminiscent of that of the other three astacins with known zymogenic and mature structures, namely crayfish astacin, human meprin β and bacterial myroilysin, but each shows specific structural characteristics. Remarkably, myroilysin lacks the PP motif and employs a cysteine instead of the aspartate to block the catalytic metal.

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“…3(e)] from the bacterium Myroides sp. CSLB8 (37 residues, 1720 Å 2 ; Xu et al, 2017). Another example is the MMP karilysin [ Fig.…”

Section: Promirolysin Latency In the Context Of Other Mpsmentioning

confidence: 99%

Structure-based mechanism of cysteine-switch latency and of catalysis by pappalysin-family metallopeptidases

Guevara

Rodríguez-Banqueri

Książek

et al. 2020

Int Union Crystallogr J

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Tannerella forsythia is an oral dysbiotic periodontopathogen involved in severe human periodontal disease. As part of its virulence factor armamentarium, at the site of colonization it secretes mirolysin, a metallopeptidase of the unicellular pappalysin family, as a zymogen that is proteolytically auto-activated extracellularly at the Ser54–Arg55 bond. Crystal structures of the catalytically impaired promirolysin point mutant E225A at 1.4 and 1.6 Å revealed that latency is exerted by an N-terminal 34-residue pro-segment that shields the front surface of the 274-residue catalytic domain, thus preventing substrate access. The catalytic domain conforms to the metzincin clan of metallopeptidases and contains a double calcium site, which acts as a calcium switch for activity. The pro-segment traverses the active-site cleft in the opposite direction to the substrate, which precludes its cleavage. It is anchored to the mature enzyme through residue Arg21, which intrudes into the specificity pocket in cleft sub-site S1′. Moreover, residue Cys23 within a conserved cysteine–glycine motif blocks the catalytic zinc ion by a cysteine-switch mechanism, first described for mammalian matrix metallopeptidases. In addition, a 1.5 Å structure was obtained for a complex of mature mirolysin and a tetradecapeptide, which filled the cleft from sub-site S1′ to S6′. A citrate molecule in S1 completed a product-complex mimic that unveiled the mechanism of substrate binding and cleavage by mirolysin, the catalytic domain of which was already preformed in the zymogen. These results, including a preference for cleavage before basic residues, are likely to be valid for other unicellular pappalysins derived from archaea, bacteria, cyanobacteria, algae and fungi, including archetypal ulilysin from Methanosarcina acetivorans. They may further apply, at least in part, to the multi-domain orthologues of higher organisms.

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Myroilysin Is a New Bacterial Member of the M12A Family of Metzincin Metallopeptidases and Is Activated by a Cysteine Switch Mechanism

Cited by 11 publications

References 63 publications

Continuous Automated Model EvaluatiOn (CAMEO) complementing the critical assessment of structure prediction in CASP12

Continuous Automated Model EvaluatiOn (CAMEO) complementing the critical assessment of structure prediction in CASP12

Zymogenic latency in an ∼250-million-year-old astacin metallopeptidase

Structure-based mechanism of cysteine-switch latency and of catalysis by pappalysin-family metallopeptidases

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