PDBsum entry 1gvz

Hydrolase

PDB id: 1gvz

Contents

Protein chain

237 a.a. *

Ligands

GOL ×3

ACT ×2

Waters ×301

* Residue conservation analysis

PDB id:

1gvz

Name:

Hydrolase

Title:

Prostate specific antigen (psa) from stallion seminal plasma

Structure:

Kallikrein-1e2. Chain: a. Synonym: kallikrein, glandular kallikrein, hpk. Ec: 3.4.21.35

Source:

Equus caballus. Horse. Organism_taxid: 9796. Organ: prostate

Resolution:

1.42Å R-factor: 0.170 R-free: 0.206

Authors:

A.L.Carvalho,L.Sanz,D.Barettino,A.Romero,J.J.Calvete,M.J.Romao

Key ref:

A.L.Carvalho et al. (2002). Crystal structure of a prostate kallikrein isolated from stallion seminal plasma: a homologue of human PSA. J Mol Biol, 322, 325-337. PubMed id: 12217694 DOI: 10.1016/S0022-2836(02)00705-2

Date:

28-Feb-02 Release date: 12-Sep-02

Protein chain

Q6H321  (KLK2_HORSE) -  Kallikrein-1E2 from Equus caballus

Seq: 261 a.a.

Struc: 237 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.3.4.21.35 - tissue kallikrein.
• Reaction: Preferential cleavage of Arg-|-Xaa bonds in small molecule substrates. Highly selective action to release kallidin (lysyl-bradykinin) from kininogen involves hydrolysis of Met-|-Xaa or Leu-|-Xaa. The rat enzyme is unusual in liberating bradykinin directly from autologous kininogens by cleavage at two Arg-|-Xaa bonds.

DOI no: 10.1016/S0022-2836(02)00705-2

J Mol Biol 322:325-337 (2002)

PubMed id: 12217694

Crystal structure of a prostate kallikrein isolated from stallion seminal plasma: a homologue of human PSA.

A.L.Carvalho, L.Sanz, D.Barettino, A.Romero, J.J.Calvete, M.J.Romão.

ABSTRACT

Prostate-specific kallikrein, a member of the gene family of serine proteases, was initially discovered in semen and is the most useful serum marker for prostate cancer diagnosis and prognosis. We report the crystal structure at 1.42A resolution of horse prostate kallikrein (HPK). This is the first structure of a serine protease purified from seminal plasma. HPK shares extensive sequence homology with human prostate-specific antigen (PSA), including a predicted chymotrypsin-like specificity, as suggested by the presence of a serine residue at position S1 of the specificity pocket. In contrast to other kallikreins, HPK shows a structurally distinct specificity pocket. Its entrance is blocked by the kallikrein loop, suggesting a possible protective or substrate-selective role for this loop. The HPK structure seems to be in an inactivated state and further processing might be required to allow the binding of substrate molecules. Crystal soaking experiments revealed a binding site for Zn(2+) and Hg(2+), two known PSA inhibitors.

Selected figure(s)

Figure 5.
Figure 5. Solid-surface representation of HPK. A consensus substrate peptide (SSYYSG), shown as ball-and-stick, was positioned, as in model structure 2PSA,[18.] in the specificity pocket of HPK in an attempt to show the necessary changes for substrate/serpin binding. In the right-hand picture, the surfaces corresponding to the kallikrein loop (Leu95A-Ser100) and to residues Trp215 to Cys220 have been removed, as well as the catalytic triad residues, which are shown as ball-and-stick and labelled red. The picture was drawn with GRASP. [53.]

Figure 7.
Figure 7. The 2F[o] -F[c] electron density map, contoured at 1.2s, around the Hg2+-binding region of the Hg-HPK structure, at 2.3 Å resolution. In the Zn-HPK structure, a zinc atom is found in the same position, coordinated by the same ligands (Asp91, His 101, His234) (see bond distances in Table 2). A probable fourth ligand is a water molecule, which is not included in the picture. His101 precedes Asp102, which, together with His57 and Ser195, form the catalytic triad. Asp91 belongs to the kallikrein loop. The picture was drawn with BOBSCRIPT [52.] and Raster3D. [51.]

The above figures are reprinted by permission from Elsevier: J Mol Biol (2002, 322, 325-337) copyright 2002.

Figures were selected by an automated process.