2009
DOI: 10.1515/bc.2009.100
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Metzincin's canonical methionine is responsible for the structural integrity of the zinc-binding site

Abstract: The metzincins constitute a subclan of metalloproteases possessing a HEXXHXXGXXH/D zinc-binding consensus sequence where the three histidines are zinc ligands and the glutamic acid is the catalytic base. A completely conserved methionine is located downstream of this motif. Families of the metzincin clan comprise, besides others, astacins, adamalysins proteases, matrix metalloproteases, and serralysins. The latter are extracellular 50 kDa proteases secreted by Gram-negative bacteria via a type I secretion syst… Show more

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Cited by 22 publications
(17 citation statements)
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“…Special mention should be given to a tight 1,4-turn situated below the catalytic zinc-site, the Met-turn, which is characterized by a strictly conserved methionine (M 147 ), both in sequence and side-chain conformation, within astacins and also all other metzincins structurally analyzed to date (Gomis -R ü th, 2009 ; Goulas et al , 2010 ;Waltersperger et al , 2010 ). It has been proposed that the Met-turn acts as a plug that inserts laterally into a core structure created by the protein segment engaged in zinc binding, thus contributing to the structural integrity that is indispensable for function, but there is still debate on its signifi cance in metzincins (Pieper et al , 1997 ;Boldt et al , 2001 ;Hege and Baumann , 2001 ;Butler et al , 2004 ;Walasek and Honek , 2005 ;P é rez et al, 2007 ;Oberholzer et al , 2009 ;Tallant et al , 2010a ). Finally, a tyrosine two positions downstream of the methionine (Y 149 ) is also engaged in zinc binding and catalysis (see also the chapter ' Active-site cleft, substrate specifi city, and zinc-binding site ' ).…”
Section: Overall Structure Of Mature Astacin Catalytic Domainsmentioning
confidence: 99%
“…Special mention should be given to a tight 1,4-turn situated below the catalytic zinc-site, the Met-turn, which is characterized by a strictly conserved methionine (M 147 ), both in sequence and side-chain conformation, within astacins and also all other metzincins structurally analyzed to date (Gomis -R ü th, 2009 ; Goulas et al , 2010 ;Waltersperger et al , 2010 ). It has been proposed that the Met-turn acts as a plug that inserts laterally into a core structure created by the protein segment engaged in zinc binding, thus contributing to the structural integrity that is indispensable for function, but there is still debate on its signifi cance in metzincins (Pieper et al , 1997 ;Boldt et al , 2001 ;Hege and Baumann , 2001 ;Butler et al , 2004 ;Walasek and Honek , 2005 ;P é rez et al, 2007 ;Oberholzer et al , 2009 ;Tallant et al , 2010a ). Finally, a tyrosine two positions downstream of the methionine (Y 149 ) is also engaged in zinc binding and catalysis (see also the chapter ' Active-site cleft, substrate specifi city, and zinc-binding site ' ).…”
Section: Overall Structure Of Mature Astacin Catalytic Domainsmentioning
confidence: 99%
“…The S-loop, which is engaged in calcium- and zinc-ion binding in some other metzincins [16], remains uncomplexed in Af AmzA. On the other hand, as the homologous archaemetzincins from Methanopyrus kandleri ( Mk AmzA) [12] and Methanocorpusculum labreanum (MlAmzA) [13], Af AmzA exhibits a second zinc-binding site located in the CTD immediately below the catalytic zinc binding site and close to the eponymous, structurally important Met-turn [10]. This element, also named Cys 4 zinc finger (Cys 4 -Zn), is composed of the four conserved cysteine residues included in the archaemetzincin fingerprint sequence HEXXHXXGXXHC 128 X 4 C 132 XMX 17 C 151 XXC 154 (Fig.…”
Section: Resultsmentioning
confidence: 99%
“…The name of this family is derived from a structurally and spatially conserved 1,4-β-turn found directly below the zinc binding site in the C-terminal domain comprising a methionine at position three in the ß-turn in all identified metzincins. Methionine-replacement studies of protease C (PrtC) from Erwinia chrysanthemi [9], [10] and ulilysin from Methanosarcina acetivorans [11] emphasized the importance of this residue for the structural and functional integrity of the active site.…”
Section: Introductionmentioning
confidence: 99%
“…The result of such insertions is that, overall, the families have evolved along separate pathways. This is reflected by sequence identities well below twilight values to discriminate between similar and dissimilar structures (20 -35%) (6), and most sequence alignment protocols only identify the extended zincbinding sequence and flanking sequence stretches (7). However, the existence of the aforementioned common structural core elements confirms that all of these families are homologous, thus underlining that structural relatedness is more conserved than sequence identity (8).…”
mentioning
confidence: 99%
“…However, major structural rearrangement and destabilization of the zinc site and an adjacent protein segment spanning ϳ80 residues were observed in the alanine mutant. In the histidine mutant crystal structure, an alternative zinc-binding site was found below the functional site (7,13). With respect to ADAMs/adamalysins, mutation of methionine in tissue necrosis factor ␣-converting enzyme to isoleucine, leucine, or serine impaired the ectodomain shedding of physiological substrates (14).…”
mentioning
confidence: 99%