Crystal structure of a prostate kallikrein isolated from stallion seminal plasma: a homologue of human PSA.
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.
Carvalho
Ana L
AL
REQUIMTE/CQFB, Departamento de Química, Fac de Ciencias e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal.
Sanz
Libia
L
Barettino
Domingo
D
Romero
Antonio
A
Calvete
Juan J
JJ
Romão
Maria J
MJ
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006736:Horses; D006801:Humans; D007610:Kallikreins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000302:isolation & purification* / Q000378:metabolism; D008297:Male; D008628:Mercury / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017430:Prostate-Specific Antigen / Q000037:antagonists & inhibitors / Q000737:chemistry*; D017433:Protein Structure, Secondary; D012661:Semen / Q000737:chemistry*; D016415:Sequence Alignment; D013379:Substrate Specificity; D015032:Zinc / Q000378:metabolism
D007610:Kallikreins; D017430:Prostate-Specific Antigen; D008628:Mercury; D015032:Zinc