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Hydrolase(metalloproteinase)
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PDB id
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1ast
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* Residue conservation analysis
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Enzyme class:
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E.C.3.4.24.21
- Astacin.
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Reaction:
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Hydrolysis of peptide bonds in substrates containing five or more amino acids, preferentially with Ala in P1', and Pro in P2'.
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Cofactor:
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Zinc
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Gene Ontology (GO) functional annotation
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Biological process
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proteolysis
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1 term
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Biochemical function
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metallopeptidase activity
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3 terms
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DOI no:
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Nature
358:164-167
(1992)
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PubMed id:
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Structure of astacin and implications for activation of astacins and zinc-ligation of collagenases.
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W.Bode,
F.X.Gomis-Rüth,
R.Huber,
R.Zwilling,
W.Stöcker.
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ABSTRACT
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Astacin, a digestive zinc-endopeptidase from the crayfish Astacus astacus L., is
the prototype for the 'astacin family', which includes mammalian
metallo-endopeptidases and developmentally regulated proteins of man, fruitfly,
frog and sea urchin. Here we report the X-ray crystal structure of astacin,
which reveals a deep active-site cleft, with the zinc at its bottom ligated by
three histidines, a water molecule and a more remote tyrosine. The third
histidine (His 102) forms part of a consensus sequence, shared not only by the
members of the astacin family, but also by otherwise sequentially unrelated
proteinases, such as vertebrate collagenases. It may therefore represent the
elusive 'third' zinc ligand in these enzymes. The amino terminus of astacin is
buried forming an internal salt-bridge with Glu 103, adjacent to His 102.
Astacin pro-forms extended at the N terminus, as observed for some 'latent'
mammalian astacin homologues, did not exhibit this 'active' conformation,
indicating an activation mechanism reminiscent of trypsin-like serine
proteinases.
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Literature references that cite this PDB file's key reference
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| |
PubMed id
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Reference
|
 |
|
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|
 |
F.X.Gomis-Rüth
(2009).
Catalytic domain architecture of metzincin metalloproteases.
|
| |
J Biol Chem, 284,
15353-15357.
|
 |
|
|
|
|
 |
J.Keifer,
B.E.Sabirzhanov,
Z.Zheng,
W.Li,
and
T.G.Clark
(2009).
Cleavage of proBDNF to BDNF by a tolloid-like metalloproteinase is required for acquisition of in vitro eyeblink classical conditioning.
|
| |
J Neurosci, 29,
14956-14964.
|
 |
|
|
|
|
 |
M.F.Wolfner
(2009).
Battle and ballet: molecular interactions between the sexes in Drosophila.
|
| |
J Hered, 100,
399-410.
|
 |
|
|
|
|
 |
O.A.Adekoya,
and
I.Sylte
(2009).
The thermolysin family (m4) of enzymes: therapeutic and biotechnological potential.
|
| |
Chem Biol Drug Des, 73,
7.
|
 |
|
|
|
|
 |
S.F.Sousa,
A.B.Lopes,
P.A.Fernandes,
and
M.J.Ramos
(2009).
The Zinc proteome: a tale of stability and functionality.
|
| |
Dalton Trans, 0,
7946-7956.
|
 |
|
|
|
|
 |
A.Tamilselvi,
and
G.Mugesh
(2008).
Zinc and antibiotic resistance: metallo-beta-lactamases and their synthetic analogues.
|
| |
J Biol Inorg Chem, 13,
1039-1053.
|
 |
|
|
|
|
 |
E.E.Sterchi,
W.Stöcker,
and
J.S.Bond
(2008).
Meprins, membrane-bound and secreted astacin metalloproteinases.
|
| |
Mol Aspects Med, 29,
309-328.
|
 |
|
|
|
|
 |
A.Schütte,
D.Lottaz,
E.E.Sterchi,
W.Stöcker,
and
C.Becker-Pauly
(2007).
Two alpha subunits and one beta subunit of meprin zinc-endopeptidases are differentially expressed in the zebrafish Danio rerio.
|
| |
Biol Chem, 388,
523-531.
|
 |
|
|
|
|
 |
B.López,
A.González,
J.Beaumont,
R.Querejeta,
M.Larman,
and
J.Díez
(2007).
Identification of a potential cardiac antifibrotic mechanism of torasemide in patients with chronic heart failure.
|
| |
J Am Coll Cardiol, 50,
859-867.
|
 |
|
|
|
|
 |
C.Wermter,
M.Höwel,
V.Hintze,
B.Bombosch,
K.Aufenvenne,
I.Yiallouros,
and
W.Stöcker
(2007).
The protease domain of procollagen C-proteinase (BMP1) lacks substrate selectivity, which is conferred by non-proteolytic domains.
|
| |
Biol Chem, 388,
513-521.
|
 |
|
|
|
|
 |
F.Möhrlen,
M.Maniura,
G.Plickert,
M.Frohme,
and
U.Frank
(2006).
Evolution of astacin-like metalloproteases in animals and their function in development.
|
| |
Evol Dev, 8,
223-231.
|
 |
|
|
|
|
 |
G.F.da Silva,
R.L.Reuille,
L.J.Ming,
and
B.T.Livingston
(2006).
Overexpression and mechanistic characterization of blastula protease 10, a metalloprotease involved in sea urchin embryogenesis and development.
|
| |
J Biol Chem, 281,
10737-10744.
|
 |
|
|
|
|
 |
S.S.Ishmael,
F.T.Ishmael,
A.D.Jones,
and
J.S.Bond
(2006).
Protease domain glycans affect oligomerization, disulfide bond formation, and stability of the meprin A metalloprotease homo-oligomer.
|
| |
J Biol Chem, 281,
37404-37415.
|
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|
|
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|
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F.T.Ishmael,
V.K.Shier,
S.S.Ishmael,
and
J.S.Bond
(2005).
Intersubunit and domain interactions of the meprin B metalloproteinase. Disulfide bonds and protein-protein interactions in the MAM and TRAF domains.
|
| |
J Biol Chem, 280,
13895-13901.
|
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|
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|
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N.Kudo,
S.Yasumasu,
I.Iuchi,
and
M.Tanokura
(2004).
Crystallization and preliminary X-ray analysis of HCE-1, a hatching enzyme of medaka fish, Oryzias latipes.
|
| |
Acta Crystallogr D Biol Crystallogr, 60,
725-726.
|
 |
|
|
|
|
 |
P.L.Tsai,
C.H.Chen,
C.J.Huang,
C.M.Chou,
and
G.D.Chang
(2004).
Purification and cloning of an endogenous protein inhibitor of carp nephrosin, an astacin metalloproteinase.
|
| |
J Biol Chem, 279,
11146-11155.
|
 |
|
|
|
|
 |
V.Quesada,
L.M.Sánchez,
J.Alvarez,
and
C.López-Otín
(2004).
Identification and characterization of human and mouse ovastacin: a novel metalloproteinase similar to hatching enzymes from arthropods, birds, amphibians, and fish.
|
| |
J Biol Chem, 279,
26627-26634.
|
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|
|
|
|
 |
C.Becker,
M.N.Kruse,
K.A.Slotty,
D.Köhler,
J.R.Harris,
S.Rösmann,
E.E.Sterchi,
and
W.Stöcker
(2003).
Differences in the activation mechanism between the alpha and beta subunits of human meprin.
|
| |
Biol Chem, 384,
825-831.
|
 |
|
|
|
|
 |
E.Liepinsh,
L.Banyai,
G.Pintacuda,
M.Trexler,
L.Patthy,
and
G.Otting
(2003).
NMR structure of the netrin-like domain (NTR) of human type I procollagen C-proteinase enhancer defines structural consensus of NTR domains and assesses potential proteinase inhibitory activity and ligand binding.
|
| |
J Biol Chem, 278,
25982-25989.
|
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|
PDB code:
|
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|
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|
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F.Möhrlen,
H.Hutter,
and
R.Zwilling
(2003).
The astacin protein family in Caenorhabditis elegans.
|
| |
Eur J Biochem, 270,
4909-4920.
|
 |
|
|
|
|
 |
J.P.Villa,
G.P.Bertenshaw,
and
J.S.Bond
(2003).
Critical amino acids in the active site of meprin metalloproteinases for substrate and peptide bond specificity.
|
| |
J Biol Chem, 278,
42545-42550.
|
 |
|
|
|
|
 |
S.Ravaud,
P.Gouet,
R.Haser,
and
N.Aghajari
(2003).
Probing the role of divalent metal ions in a bacterial psychrophilic metalloprotease: binding studies of an enzyme in the crystalline state by x-ray crystallography.
|
| |
J Bacteriol, 185,
4195-4203.
|
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|
PDB codes:
|
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|
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|
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B.A.Doll,
J.P.Villa,
F.T.Ishmael,
and
J.S.Bond
(2002).
Zinc ligands in an astacin family metalloprotease meprin A.
|
| |
Biol Chem, 383,
1167-1173.
|
 |
|
|
|
|
 |
J.Pei,
and
N.V.Grishin
(2002).
Breaking the singleton of germination protease.
|
| |
Protein Sci, 11,
691-697.
|
 |
|
|
|
|
 |
K.F.Huang,
S.H.Chiou,
T.P.Ko,
J.M.Yuann,
and
A.H.Wang
(2002).
The 1.35 A structure of cadmium-substituted TM-3, a snake-venom metalloproteinase from Taiwan habu: elucidation of a TNFalpha-converting enzyme-like active-site structure with a distorted octahedral geometry of cadmium.
|
| |
Acta Crystallogr D Biol Crystallogr, 58,
1118-1128.
|
 |
|
PDB code:
|
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|
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|
 |
S.Rösmann,
D.Hahn,
D.Lottaz,
M.N.Kruse,
W.Stöcker,
and
E.E.Sterchi
(2002).
Activation of human meprin-alpha in a cell culture model of colorectal cancer is triggered by the plasminogen-activating system.
|
| |
J Biol Chem, 277,
40650-40658.
|
 |
|
|
|
|
 |
A.Hallmann,
P.Amon,
K.Godl,
M.Heitzer,
and
M.Sumper
(2001).
Transcriptional activation by the sexual pheromone and wounding: a new gene family from Volvox encoding modular proteins with (hydroxy)proline-rich and metalloproteinase homology domains.
|
| |
Plant J, 26,
583-593.
|
 |
|
|
|
|
 |
F.Möhrlen,
S.Baus,
A.Gruber,
H.R.Rackwitz,
M.Schnölzer,
G.Vogt,
and
R.Zwilling
(2001).
Activation of pro-astacin. Immunological and model peptide studies on the processing of immature astacin, a zinc-endopeptidase from the crayfish Astacus astacus.
|
| |
Eur J Biochem, 268,
2540-2546.
|
 |
|
|
|
|
 |
T.Hori,
T.Kumasaka,
M.Yamamoto,
N.Nonaka,
N.Tanaka,
Y.Hashimoto,
U.Ueki,
and
K.Takio
(2001).
Structure of a new 'aspzincin' metalloendopeptidase from Grifola frondosa: implications for the catalytic mechanism and substrate specificity based on several different crystal forms.
|
| |
Acta Crystallogr D Biol Crystallogr, 57,
361-368.
|
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|
PDB codes:
|
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|
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K.A.Crandall,
D.J.Harris,
and
J.W.Fetzner
(2000).
The monophyletic origin of freshwater crayfish estimated from nuclear and mitochondrial DNA sequences.
|
| |
Proc Biol Sci, 267,
1679-1686.
|
 |
|
|
|
|
 |
I.Abbaszade,
R.Q.Liu,
F.Yang,
S.A.Rosenfeld,
O.H.Ross,
J.R.Link,
D.M.Ellis,
M.D.Tortorella,
M.A.Pratta,
J.M.Hollis,
R.Wynn,
J.L.Duke,
H.J.George,
M.C.Hillman,
K.Murphy,
B.H.Wiswall,
R.A.Copeland,
C.P.Decicco,
R.Bruckner,
H.Nagase,
Y.Itoh,
R.C.Newton,
R.L.Magolda,
J.M.Trzaskos,
and
T.C.Burn
(1999).
Cloning and characterization of ADAMTS11, an aggrecanase from the ADAMTS family.
|
| |
J Biol Chem, 274,
23443-23450.
|
 |
|
|
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|
 |
K.Fukasawa,
K.M.Fukasawa,
H.Iwamoto,
J.Hirose,
and
M.Harada
(1999).
The HELLGH motif of rat liver dipeptidyl peptidase III is involved in zinc coordination and the catalytic activity of the enzyme.
|
| |
Biochemistry, 38,
8299-8303.
|
 |
|
|
|
|
 |
W.Bode,
C.Fernandez-Catalan,
F.Grams,
F.X.Gomis-Rüth,
H.Nagase,
H.Tschesche,
and
K.Maskos
(1999).
Insights into MMP-TIMP interactions.
|
| |
Ann N Y Acad Sci, 878,
73-91.
|
 |
|
|
|
|
 |
X.Zhu,
M.Teng,
and
L.Niu
(1999).
Structure of acutolysin-C, a haemorrhagic toxin from the venom of Agkistrodon acutus, providing further evidence for the mechanism of the pH-dependent proteolytic reaction of zinc metalloproteinases.
|
| |
Acta Crystallogr D Biol Crystallogr, 55,
1834-1841.
|
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|
PDB code:
|
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|
 |
C.Meneghini,
and
S.Morante
(1998).
The active site structure of tetanus neurotoxin resolved by multiple scattering analysis in X-Ray absorption spectroscopy.
|
| |
Biophys J, 75,
1953-1963.
|
 |
|
|
|
|
 |
E.Schlagenhauf,
R.Etges,
and
P.Metcalf
(1998).
The crystal structure of the Leishmania major surface proteinase leishmanolysin (gp63).
|
| |
Structure, 6,
1035-1046.
|
 |
|
PDB code:
|
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|
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|
 |
H.H.Thorp
(1998).
Bioinorganic chemistry and drug design: here comes zinc again.
|
| |
Chem Biol, 5,
R125-R127.
|
 |
|
|
|
|
 |
I.L.Alberts,
K.Nadassy,
and
S.J.Wodak
(1998).
Analysis of zinc binding sites in protein crystal structures.
|
| |
Protein Sci, 7,
1700-1716.
|
 |
|
|
|
|
 |
A.Chestukhin,
L.Litovchick,
K.Muradov,
M.Batkin,
and
S.Shaltiel
(1997).
Unveiling the substrate specificity of meprin beta on the basis of the site in protein kinase A cleaved by the kinase splitting membranal proteinase.
|
| |
J Biol Chem, 272,
3153-3160.
|
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|
|
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|
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C.H.Hung,
H.R.Huang,
C.J.Huang,
F.L.Huang,
and
G.D.Chang
(1997).
Purification and cloning of carp nephrosin, a secreted zinc endopeptidase of the astacin family.
|
| |
J Biol Chem, 272,
13772-13778.
|
 |
|
|
|
|
 |
G.D.Johnson,
and
J.S.Bond
(1997).
Activation mechanism of meprins, members of the astacin metalloendopeptidase family.
|
| |
J Biol Chem, 272,
28126-28132.
|
 |
|
|
|
|
 |
M.L.Brader,
N.C.Kaarsholm,
S.E.Harnung,
and
M.F.Dunn
(1997).
Ligand perturbation effects on a pseudotetrahedral Co(II)(His)3-ligand site. A magnetic circular dichroism study of the Co(II)-substituted insulin hexamer.
|
| |
J Biol Chem, 272,
1088-1094.
|
 |
|
|
|
|
 |
S.Lee,
D.E.Solow-Cordero,
E.Kessler,
K.Takahara,
and
D.S.Greenspan
(1997).
Transforming growth factor-beta regulation of bone morphogenetic protein-1/procollagen C-proteinase and related proteins in fibrogenic cells and keratinocytes.
|
| |
J Biol Chem, 272,
19059-19066.
|
 |
|
|
|
|
 |
T.Nonaka,
N.Dohmae,
Y.Hashimoto,
and
K.Takio
(1997).
Amino acid sequences of metalloendopeptidases specific for acyl-lysine bonds from Grifola frondosa and Pleurotus ostreatus fruiting bodies.
|
| |
J Biol Chem, 272,
30032-30039.
|
 |
|
|
|
|
 |
V.Villeret,
J.P.Chessa,
C.Gerday,
and
J.Van Beeumen
(1997).
Preliminary crystal structure determination of the alkaline protease from the Antarctic psychrophile Pseudomonas aeruginosa.
|
| |
Protein Sci, 6,
2462-2464.
|
 |
|
|
|
|
 |
A.Cleasby,
A.Wonacott,
T.Skarzynski,
R.E.Hubbard,
G.J.Davies,
A.E.Proudfoot,
A.R.Bernard,
M.A.Payton,
and
T.N.Wells
(1996).
The x-ray crystal structure of phosphomannose isomerase from Candida albicans at 1.7 angstrom resolution.
|
| |
Nat Struct Biol, 3,
470-479.
|
 |
|
PDB code:
|
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|
|
|
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|
 |
F.Grams,
V.Dive,
A.Yiotakis,
I.Yiallouros,
S.Vassiliou,
R.Zwilling,
W.Bode,
and
W.Stöcker
(1996).
Structure of astacin with a transition-state analogue inhibitor.
|
| |
Nat Struct Biol, 3,
671-675.
|
 |
|
PDB codes:
|
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|
 |
P.Marchand,
M.Volkmann,
and
J.S.Bond
(1996).
Cysteine mutations in the MAM domain result in monomeric meprin and alter stability and activity of the proteinase.
|
| |
J Biol Chem, 271,
24236-24241.
|
 |
|
|
|
|
 |
S.Morante,
L.Furenlid,
G.Schiavo,
F.Tonello,
R.Zwilling,
and
C.Montecucco
(1996).
X-ray absorption spectroscopy study of zinc coordination in tetanus neurotoxin, astacin, alkaline protease and thermolysin.
|
| |
Eur J Biochem, 235,
606-612.
|
 |
|
|
|
|
 |
V.Dhanaraj,
Q.Z.Ye,
L.L.Johnson,
D.J.Hupe,
D.F.Ortwine,
J.B.Dunbar,
J.R.Rubin,
A.Pavlovsky,
C.Humblet,
and
T.L.Blundell
(1996).
X-ray structure of a hydroxamate inhibitor complex of stromelysin catalytic domain and its comparison with members of the zinc metalloproteinase superfamily.
|
| |
Structure, 4,
375-386.
|
 |
|
|
|
|
 |
A.Beaumont,
M.J.O'Donohue,
N.Paredes,
N.Rousselet,
M.Assicot,
C.Bohuon,
M.C.Fournié-Zaluski,
and
B.P.Roques
(1995).
The role of histidine 231 in thermolysin-like enzymes. A site-directed mutagenesis study.
|
| |
J Biol Chem, 270,
16803-16808.
|
 |
|
|
|
|
 |
A.L.Finelli,
T.Xie,
C.A.Bossie,
R.K.Blackman,
and
R.W.Padgett
(1995).
The tolkin gene is a tolloid/BMP-1 homologue that is essential for Drosophila development.
|
| |
Genetics, 141,
271-281.
|
 |
|
|
|
|
 |
C.Montecucco,
and
G.Schiavo
(1995).
Structure and function of tetanus and botulinum neurotoxins.
|
| |
Q Rev Biophys, 28,
423-472.
|
 |
|
|
|
|
 |
D.Soler,
T.Nomizu,
W.E.Brown,
Y.Shibata,
and
D.S.Auld
(1995).
Matrilysin: expression, purification, and characterization.
|
| |
J Protein Chem, 14,
511-520.
|
 |
|
|
|
|
 |
F.Grams,
P.Reinemer,
J.C.Powers,
T.Kleine,
M.Pieper,
H.Tschesche,
R.Huber,
and
W.Bode
(1995).
X-ray structures of human neutrophil collagenase complexed with peptide hydroxamate and peptide thiol inhibitors. Implications for substrate binding and rational drug design.
|
| |
Eur J Biochem, 228,
830-841.
|
 |
|
PDB codes:
|
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|
|
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|
 |
H.Ostolaza,
A.Soloaga,
and
F.M.Goñi
(1995).
The binding of divalent cations to Escherichia coli alpha-haemolysin.
|
| |
Eur J Biochem, 228,
39-44.
|
 |
|
|
|
|
 |
H.Zaima,
N.Ueyama,
H.Adachi,
and
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(1995).
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