PDBsum entry 3aig

Hydrolase/hydrolase inhibitor

PDB id

3aig

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Contents

			Protein chain

					201 a.a. *

			Ligands

					SO4


					0ZC

			Metals

					_ZN


					_CA

			Waters ×129

* Residue conservation analysis

PDB id:

3aig

Links

Name:

Hydrolase/hydrolase inhibitor

Title:

Adamalysin ii with peptidomimetic inhibitor pol656

Structure:

Adamalysin ii. Chain: a. Ec: 3.4.24.46

Source:

Crotalus adamanteus. Eastern diamondback rattlesnake. Organism_taxid: 8729. Secretion: venom

Biol. unit:

Dimer (from PQS)

Resolution:

2.80Å

R-factor:

0.194

Authors:

F.X.Gomis-Rueth,E.F.Meyer,L.F.Kress,V.Politi

Key ref:

F.X.Gomis-Rüth et al. (1998). Structures of adamalysin II with peptidic inhibitors. Implications for the design of tumor necrosis factor alpha convertase inhibitors. Protein Sci, 7, 283-292. PubMed id: 9521103 DOI: 10.1002/pro.5560070207

Date:

12-Oct-97

Release date:

15-Apr-98

PROCHECK

	Headers

	References

Protein chain

P34179 (VM12_CROAD) - Snake venom metalloproteinase adamalysin-2 from Crotalus adamanteus

Seq: Struc:					203 a.a. 201 a.a.*

Key:

PfamA domain

Secondary structure

CATH domain

* PDB and UniProt seqs differ at 21 residue positions (black crosses)



		Enzyme reactions

Enzyme class:

E.C.3.4.24.46 - adamalysin.

[IntEnz] [ExPASy] [KEGG] [BRENDA]

Reaction:

Cofactor:

Zn(2+)

DOI no: 10.1002/pro.5560070207	Protein Sci 7:283-292 (1998)
PubMed id: 9521103

Structures of adamalysin II with peptidic inhibitors. Implications for the design of tumor necrosis factor alpha convertase inhibitors.
F.X.Gomis-Rüth, E.F.Meyer, L.F.Kress, V.Politi.

ABSTRACT

Crotalus adamanteus snake venom adamalysin II is the structural prototype of the adamalysin or ADAM family comprising proteolytic domains of snake venom metalloproteinases, multimodular mammalian reproductive tract proteins, and tumor necrosis factor alpha convertase, TACE, involved in the release of the inflammatory cytokine, TNFalpha. The structure of adamalysin II in noncovalent complex with two small-molecule right-hand side peptidomimetic inhibitors (Pol 647 and Pol 656) has been solved using X-ray diffraction data up to 2.6 and 2.8 A resolution. The inhibitors bind to the S'-side of the proteinase, inserting between two protein segments, establishing a mixed parallel-antiparallel three-stranded beta-sheet and coordinate the central zinc ion in a bidentate manner via their two C-terminal oxygen atoms. The proteinase-inhibitor complexes are described in detail and are compared with other known structures. An adamalysin-based model of the active site of TACE reveals that these small molecules would probably fit into the active site cleft of this latter metalloproteinase, providing a starting model for the rational design of TACE inhibitors.

Literature references that cite this PDB file's key reference

PubMed id

Reference

17976018

C.Tallant, R.García-Castellanos, A.Marrero, F.Canals, Y.Yang, J.L.Reymond, M.Solà, U.Baumann, and F.X.Gomis-Rüth (2007).
Activity of ulilysin, an archaeal PAPP-A-related gelatinase and IGFBP protease.

Biol Chem, 388, 1243-1253.

16790761

D.N.Meli, R.S.Coimbra, D.G.Erhart, G.Loquet, C.L.Bellac, M.G.Täuber, U.Neumann, and S.L.Leib (2006).
Doxycycline reduces mortality and injury to the brain and cochlea in experimental pneumococcal meningitis.

Infect Immun, 74, 3890-3896.

12789686

C.T.Supuran, A.Casini, and A.Scozzafava (2003).
Protease inhibitors of the sulfonamide type: anticancer, antiinflammatory, and antiviral agents.

Med Res Rev, 23, 535-558.

12071970

K.F.Huang, S.H.Chiou, T.P.Ko, and A.H.Wang (2002).
Determinants of the inhibition of a Taiwan habu venom metalloproteinase by its endogenous inhibitors revealed by X-ray crystallography and synthetic inhibitor analogues.

Eur J Biochem, 269, 3047-3056.

PDB codes:

1kug 1kui 1kuk

12077431

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:

1kuf

11468397

D.H.Souza, H.S.Selistre-de-Araujo, A.M.Moura-da-Silva, M.S.Della-Casa, G.Oliva, and R.C.Garratt (2001).
Crystallization and preliminary X-ray analysis of jararhagin, a metalloproteinase/disintegrin from Bothrops jararaca snake venom.

Acta Crystallogr D Biol Crystallogr, 57, 1135-1137.

10531480

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.

PDB code:

1qua

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.