1.70 angstrom X-ray structure of human apo kallikrein 1: Structural changes upon peptide inhibitor/substrate binding

Show simple item record

dc.contributor.author Laxmikanthan, G.
dc.contributor.author Blaber, S. I.
dc.contributor.author Bernett, M. J.
dc.contributor.author Scarisbrick, I. A.
dc.contributor.author Juliano, M. A.
dc.contributor.author Blaber, M.
dc.date.accessioned 2016-01-24T12:37:42Z
dc.date.available 2016-01-24T12:37:42Z
dc.date.issued 2005-03-01
dc.identifier http://dx.doi.org/10.1002/prot.20368
dc.identifier.citation Proteins-structure Function and Bioinformatics. Hoboken: Wiley-liss, v. 58, n. 4, p. 802-814, 2005.
dc.identifier.issn 0887-3585
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/28170
dc.description.abstract Human kallikreins are serine proteases that comprise a recently identified large and closely related 15-member family. the kallikreins include both regulatory- and degradative-type proteases, impacting a variety of physiological processes including regulation of blood pressure, neuronal health, and the inflammatory response. While the function of the majority of the kallikreins remains to be elucidated, two members are useful biomarkers for prostate cancer and several others are potentially useful biomarkers for breast cancer, Alzheimer's, and Parkinson's disease. Human tissue kallikrein (human K1) is the best functionally characterized member of this family, and is known to play an important role in blood pressure regulation. As part of this function, human K1 exhibits unique dual-substrate specificity in hydrolyzing low molecular weight kininogen between both Arg-Ser and Met-Lys sequences. We report the X-ray crystal structure of mature, active recombinant human apo K1 at 1.70 Angstrom resolution. the active site exhibits structural features intermediate between that of apo and pro forms of known kallikrein structures. the S2 to S2' pockets demonstrate a variety of conformational changes in comparison to the porcine homolog of K1 in complex with peptide inhibitors, including the displacement of an extensive solvent network. These results indicate that the binding of a peptide substrate contributes to a structural rearrangement of the active-site Ser 195 resulting in a catalytically competent juxtaposition with the active-site His 57. the solvent networks within the S1 and S1' pockets suggest how the Arg-Ser and Met-Lys dual substrate specificity of human K1 is accommodated. Proteins (C) 2005 Wiley-Liss, Inc. en
dc.format.extent 802-814
dc.language.iso eng
dc.publisher Wiley-Blackwell
dc.relation.ispartof Proteins-structure Function and Bioinformatics
dc.rights Acesso restrito
dc.subject kallikrein en
dc.subject serine protease en
dc.subject substrate specificity en
dc.subject solvent structure en
dc.subject induced fit en
dc.title 1.70 angstrom X-ray structure of human apo kallikrein 1: Structural changes upon peptide inhibitor/substrate binding en
dc.type Artigo
dc.rights.license http://olabout.wiley.com/WileyCDA/Section/id-406071.html
dc.contributor.institution Florida State Univ
dc.contributor.institution Mayo Clin & Mayo Grad Sch Med
dc.contributor.institution Universidade Federal de São Paulo (UNIFESP)
dc.description.affiliation Florida State Univ, Inst Mol Biophys, Kasha Lab 406, Tallahassee, FL 32306 USA
dc.description.affiliation Florida State Univ, Dept Chem & Biochem, Tallahassee, FL 32306 USA
dc.description.affiliation Mayo Clin & Mayo Grad Sch Med, Mol Neurosci Program, Rochester, MN 55901 USA
dc.description.affiliation Mayo Clin & Mayo Grad Sch Med, Dept Neurol, Rochester, MN 55901 USA
dc.description.affiliation Mayo Clin & Mayo Grad Sch Med, Dept Phys Med & Rehabil, Rochester, MN 55901 USA
dc.description.affiliation Universidade Federal de São Paulo, Dept Biophys, Escola Paulista Med, São Paulo, Brazil
dc.description.affiliationUnifesp Universidade Federal de São Paulo, Dept Biophys, Escola Paulista Med, São Paulo, Brazil
dc.identifier.doi 10.1002/prot.20368
dc.description.source Web of Science
dc.identifier.wos WOS:000227106100004



File

File Size Format View

There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record

Search


Browse

Statistics

My Account