Cloning of cDNA encoding a new peptide C-terminal α-amidating enzyme having a putative membrane-spanning domain from Xenopuslaevis skin

Ohsuye, Kazuhiro; Kitano, Katsuhiko; Wada, Yukari; Fuchimura, Kayoko; Tanaka, Shoji; Mizuno, Kensaku; Matsuo, Hisayuki

doi:10.1016/0006-291x(88)90767-x

Cited by 65 publications

(23 citation statements)

References 9 publications

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“…Our initial search of the protein databases with the tryptic peptide containing the attachment site of B-ethinyltyramine gave a score of 96°7o identity over 25 amino acids with human DBH and 47°7o over 17 amino acids with the peptide ce-amidating enzyme from the frog Xenopus laevis [6]. When the FASTA search was repeated using the entire human DBH sequence the only match with a significant score over an extended length of polypeptide chain was with frog PAM.…”

Section: Resultsmentioning

confidence: 99%

“…Between rat, bovine and frog PAMs this section is highly conserved and tissue-specific truncated forms of active PAM of between 300 and 350 residues can be produced in vivo by alternative mRNA splicing and/or endoproteolytic processing [8]. Residues 38 to 381 of frog PAM expressed in E. coli show amidating activity in vitro [6]. Independent evidence for an extended catalytic domain in DBH comes from attachment sites of mechanism-based inhibitors.…”

Section: Discussionmentioning

confidence: 99%

“…The attachment site for ~-ethinyltyramine at His 398 was isolated as a 25 residue tryptic peptide that included a putative copper binding site [5]. A search of the protein sequence data banks with this peptide revealed, in addition to a match with the corresponding section from human DBH, a similarity with peptide C-terminal ce-amidating enzyme (PAM; EC 1.14.17.3) from Xenopus laevis [6].…”

Section: Introductionmentioning

confidence: 99%

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Sequence similarity between dopamine β‐hydroxylase and peptide α‐amidating enzyme: Evidence for a conserved catalytic domain

Southan¹,

Kruse²

1989

FEBS Letters

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A comparison of human dopamine fl-hydroxylase (EC 1.14.17.1) with bovine peptide C-terminal ~t-amidating enzyme (EC 1.14.17.3), revealed a 28% identity extending throughout a common catalytic domain of approximately 270 residues. The shared biochemical properties of these two enzymes from neurosecretory granules suggests that the sequence similarity reflects a genuine homology and provides a structural basis for a new family of copper type II, ascorbate-dependent monooxygenases.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Sequence similarity between dopamine β‐hydroxylase and peptide α‐amidating enzyme: Evidence for a conserved catalytic domain

Southan¹,

Kruse²

1989

FEBS Letters

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“…3. The N-terminal and partial sequence analysis indicated that the structure of PHL is similar to that of the C-terminal portion of AE-I1 [7] (12 amino acid substitutions among the 286 residues sequenced). However, the C-terminal residue of PHL could not be identified.…”

Section: Partial Amino Acid Sequencingmentioning

confidence: 95%

“…AE-I1 cDNA was isolated from the X . laevis skin cDNA library [I41 using a synthetic oligonucleotide probe prepared according to the known sequence [7]. Specific primers for polymerase chain reaction experiments and for DNA sequencing were prepared by using a DNA synthesizer (model 38319, Applied Biosystems).…”

Section: Methodsmentioning

confidence: 99%

Purification and cDNA cloning of Xenopus laevis skin peptidylhydroxyglycine N‐C lyase, catalyzing the second reaction of C‐terminal α‐amidation

Iwasaki

Kawahara

Shimoi

et al. 1991

European Journal of Biochemistry

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The a-amidation of glycine-extended peptides is a two-step reaction catalyzed by peptidylglycine a-hydroxylating monooxygenase (PHM) and peptidylhydroxyglycine N-C lyase (PHL). PHL was purified to homogeneity from Xenopus luevis skin and its partial amino acid sequence (including the N-terminal 35 residues) was determined. A cDNA, termed AE-111, encoding X. luevis PHL, was cloned and its complete nucleotide sequence was determined. It was found that the cDNA codes for a 935-residue precursor protein (AE-I11 protein), containing the PHM and PHL sequences at its N terminus and C terminus, respectively. The PHM sequence in AE-111 protein is completely identical to that deduced from the nucleotide sequence of X . luevis AE-I cDNA, which encodes only PHM, except that the AE-I protein has an extra 10 residues at its C terminus. It is suggested that AE-I and AE-111 mRNA are encoded by the same gene and produced by alternative splicing.Many biologically active peptides are amidated at the C terminus and, in most cases, this is essential for their functions. These peptides are enzymatically synthesized from glycineextended peptides in the presence of molecular oxygen, Cu2+ and L-ascorbate [I -41.X-CO-NH-CH,-COOH 02, C u 2~;~c o r b a t~ X-CO-NH2

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Peptidylglycine α‐Hydroxylating Monooxygenase (PHM)

Rudzka

Chufán

Eipper

et al. 2004

Handbook of Metalloproteins

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Numerous peptides function as hormones, neurotransmitters, and growth factors. Enzymatic α‐amidation is a biologically important posttranslational modification of the C‐terminus of many of these peptides. This modification alters the biological properties and enhances the stability of the peptides toward digestion by carboxypeptidases. Peptidylglycine α‐hydroxylating monooxygenase (PHM) is an ascorbate and copper‐dependent catalytic domain of an α‐amidating enzyme (peptidylglycine α‐amidating monooxygenase, PAM) that catalyzes the stereospecific hydroxylation of an α‐carbon of a terminal glycine residue, the first step in the amidation reaction. This reaction is followed by cleavage of the glycine N Cα bond, which is carried out by the second PAM catalytic domain, peptidyl‐α‐hydroxyglycine α‐amidating lyase (PAL). Detailed structural studies of PHM revealed that its catalytic core binds two copper ions that support the oxygenation reaction by cycling through Cu(II)/Cu(I) oxidation states. These two Cu ions (Cu H and Cu M ) are located 11 Å apart and are separated by a solvent‐accessible cleft. The monooxygenation reaction requires the two‐electron activation of molecular oxygen, which is achieved by the binding of O 2 to a single Cu(I) center (Cu M ). Formation of this complex is dependent upon the presence of a peptidylglycine substrate and a reducing agent (ascorbate). Since the resting state of the enzyme contains two Cu(II) ions, the catalytic reaction requires transfer of two electrons from the reducing agent to the metal centers, and from the reduced copper ions to dioxygen. The reduced oxygen species then carries out the stereospecific hydroxylation of glycine after abstraction of the pro‐S hydrogen from Cα. Although, the structure and function of PHM have been broadly studied, the pathway of its electron transfer, the nature of the metal‐oxygen species, and details of the mechanism are still being investigated.

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Cloning of cDNA encoding a new peptide C-terminal α-amidating enzyme having a putative membrane-spanning domain from Xenopuslaevis skin

Cited by 65 publications

References 9 publications

Sequence similarity between dopamine β‐hydroxylase and peptide α‐amidating enzyme: Evidence for a conserved catalytic domain

Sequence similarity between dopamine β‐hydroxylase and peptide α‐amidating enzyme: Evidence for a conserved catalytic domain

Purification and cDNA cloning of Xenopus laevis skin peptidylhydroxyglycine N‐C lyase, catalyzing the second reaction of C‐terminal α‐amidation

Peptidylglycine α‐Hydroxylating Monooxygenase (PHM)

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